Table of Contents Author Guidelines Submit a Manuscript
Journal of Toxicology
Volume 2012, Article ID 756358, 21 pages
http://dx.doi.org/10.1155/2012/756358
Review Article

Towards Therapeutic Applications of Arthropod Venom K+-Channel Blockers in CNS Neurologic Diseases Involving Memory Acquisition and Storage

1Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade de Brasília, 70910-900 Brasília, DF, Brazil
2Universidade Católica de Brasília, 71966-700 Brasília, DF, Brazil

Received 29 December 2011; Accepted 8 February 2012

Academic Editor: Yonghua Ji

Copyright © 2012 Christiano D. C. Gati et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. Nadel and O. Hardt, “Update on memory systems and processes,” Neuropsychopharmacology, vol. 36, no. 1, pp. 251–273, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. I. Morgado-Bernal, “Learning and memory consolidation: linking molecular and behavioral data,” Neuroscience, vol. 176, pp. 12–19, 2011. View at Publisher · View at Google Scholar
  3. J. Kim and D. A. Hoffman, “Potassium channels: newly found players in synaptic plasticity,” Neuroscientist, vol. 14, no. 3, pp. 276–286, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. W. A. Coetzee, Y. Amarillo, J. Chiu et al., “Molecular diversity of K+ channels,” Annals of the New York Academy of Sciences, vol. 868, pp. 233–285, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. S. I. V. Judge, P. J. Smith, P. E. Stewart, and C. T. Bever, “Potassium channel blockers and openers as CNS neurologic therapeutic agents,” Recent Patents on CNS Drug Discovery, vol. 2, no. 3, pp. 200–228, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. G. A. Gutman, K. G. Chandy, S. Grissmer et al., “International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels,” Pharmacological Reviews, vol. 57, no. 4, pp. 473–508, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. A. D. Wei, G. A. Gutman, R. Aldrich, K. G. Chandy, S. Grissmer, and H. Wulff, “International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels,” Pharmacological Reviews, vol. 57, no. 4, pp. 463–472, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. Y. Kubo, J. P. Adelman, D. E. Clapham et al., “International union of pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels,” Pharmacological Reviews, vol. 57, no. 4, pp. 509–526, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. S. A. N. Goldstein, D. A. Bayliss, D. Kim, F. Lesage, L. D. Plant, and S. Rajan, “International union of pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels,” Pharmacological Reviews, vol. 57, no. 4, pp. 527–540, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. C. Miller, “An overview of the potassium channel family,” Genome biology, vol. 1, no. 4, Article ID REVIEWS0004, 2000. View at Google Scholar · View at Scopus
  11. G. Yellen, “The voltage-gated potassium channels and their relatives,” Nature, vol. 419, no. 6902, pp. 35–42, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. K. L. Magleby, “Gating mechanism of BK (Slo1) channels: so near, yet so far,” Journal of General Physiology, vol. 121, no. 2, pp. 81–96, 2003. View at Publisher · View at Google Scholar · View at Scopus
  13. F. H. Yu, V. Yarov-Yarovoy, G. A. Gutman, and W. A. Catterall, “Overview of molecular relationships in the voltage-gated ion channel superfamily,” Pharmacological Reviews, vol. 57, no. 4, pp. 387–395, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. S. B. Long, E. B. Campbell, and R. MacKinnon, “Crystal structure of a mammalian voltage-dependent Shaker family K+ channel,” Science, vol. 309, no. 5736, pp. 897–903, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. J. L. Moreland, A. Gramada, O. V. Buzko, Q. Zhang, and P. E. Bourne, “The Molecular Biology Toolkit (MBT): a modular platform fro developing molecular visualization applications,” BMC Bioinformatics, vol. 6, article no. 21, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. C. Gu and J. Barry, “Function and mechanism of axonal targeting of voltage-sensitive potassium channels,” Progress in Neurobiology, vol. 94, no. 2, pp. 115–132, 2011. View at Publisher · View at Google Scholar
  17. M. Weiser, E. Vega-Saenz De Miera, C. Kentros et al., “Differential expression of Shaw-related K+ channels in the rat central nervous system,” Journal of Neuroscience, vol. 14, no. 3, pp. 949–972, 1994. View at Google Scholar · View at Scopus
  18. P. Serôdio and B. Rudy, “Differential expression of Kv4 K+ channel subunits mediating subthreshold transient K+ (A-type) currents in rat brain,” Journal of Neurophysiology, vol. 79, no. 2, pp. 1081–1091, 1998. View at Google Scholar · View at Scopus
  19. M. J. Saganich, E. Machado, and B. Rudy, “Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain,” Journal of Neuroscience, vol. 21, no. 13, pp. 4609–4624, 2001. View at Google Scholar · View at Scopus
  20. R. Luján, C. D. C. De La Vega, E. D. Del Toro, J. J. Ballesta, M. Criado, and J. M. Juiz, “Immunohistochemical localization of the voltage-gated potassium channel subunit Kv1.4 in the central nervous system of the adult rat,” Journal of Chemical Neuroanatomy, vol. 26, no. 3, pp. 209–224, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. H. G. Knaus, C. Schwarzer, R. O. A. Koch et al., “Distribution of high-conductance Ca2+-activated K+ channels in rat brain: targeting to axons and nerve terminals,” Journal of Neuroscience, vol. 16, no. 3, pp. 955–963, 1996. View at Google Scholar · View at Scopus
  22. U. Sausbier, M. Sausbier, C. A. Sailer et al., “Ca2+-activated K+ channels of the BK-type in the mouse brain,” Histochemistry and Cell Biology, vol. 125, no. 6, pp. 725–741, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Stocker and P. Pedarzani, “Differential distribution of three Ca2+-activated K+ channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system,” Molecular and Cellular Neurosciences, vol. 15, no. 5, pp. 476–493, 2000. View at Publisher · View at Google Scholar · View at Scopus
  24. C. A. Sailer, H. Hu, W. A. Kaufmann et al., “Regional differences in distribution and functional expression of small-conductance Ca2+-activated K+ channels in rat brain,” Journal of Neuroscience, vol. 22, no. 22, pp. 9698–9707, 2002. View at Google Scholar · View at Scopus
  25. B. Mpari, L. Sreng, I. Regaya, and C. Mourre, “Small-conductance Ca2+-activated K+ channels: Heterogeneous affinity in rat brain structures and cognitive modulation by specific blockers,” European Journal of Pharmacology, vol. 589, no. 1–3, pp. 140–148, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. Y. Horio, K. I. Morishige, N. Takahashi, and Y. Kurachi, “Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain: comparison of IRK2 with IRK1 and IRK3,” FEBS Letters, vol. 379, no. 3, pp. 239–243, 1996. View at Publisher · View at Google Scholar · View at Scopus
  27. C. Karschin, E. Dißmann, W. Stühmer, and A. Karschin, “IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain,” Journal of Neuroscience, vol. 16, no. 11, pp. 3559–3570, 1996. View at Google Scholar · View at Scopus
  28. T. Miyashita and Y. Kubo, “Localization and developmental changes of the expression of two inward rectifying K+-channel proteins in the rat brain,” Brain Research, vol. 750, no. 1-2, pp. 251–263, 1997. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Zhou, O. Tanaka, M. Suzuki et al., “Localization of pore-forming subunit of the ATP-sensitive K+-channel, Kir6.2, in rat brain neurons and glial cells,” Molecular Brain Research, vol. 101, no. 1-2, pp. 23–32, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. G. J. Hervieu, J. E. Cluderay, C. W. Gray et al., “Distribution and expression of TREK-1, a two-pore-domain potassium channel, in the adult rat CNS,” Neuroscience, vol. 103, no. 4, pp. 899–919, 2001. View at Publisher · View at Google Scholar · View at Scopus
  31. E. M. Talley, G. Solórzano, Q. Lei, D. Kim, and D. A. Bayliss, “CNS distribution of members of the two-pore-domain (KCNK) potassium channel family,” Journal of Neuroscience, vol. 21, no. 19, pp. 7491–7505, 2001. View at Google Scholar · View at Scopus
  32. A. Mathie, J. R. A. Wooltorton, and C. S. Watkins, “Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents,” General Pharmacology, vol. 30, no. 1, pp. 13–24, 1998. View at Publisher · View at Google Scholar · View at Scopus
  33. G. M. Lipkind and H. A. Fozzard, “A model of scorpion toxin binding to voltage-gated K+ channels,” Journal of Membrane Biology, vol. 158, no. 3, pp. 187–196, 1997. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Grunnet, B. S. Jensen, S. P. Olesen, and D. A. Klaerke, “Apamin interacts with all subtypes of cloned small-conductance Ca2+-activated K+ channels,” Pflugers Archiv European Journal of Physiology, vol. 441, no. 4, pp. 544–550, 2001. View at Publisher · View at Google Scholar · View at Scopus
  35. A. L. Harvey, K. N. Bradley, S. A. Cochran et al., “What can toxins tell us for drug discovery?” Toxicon, vol. 36, no. 11, pp. 1635–1640, 1998. View at Publisher · View at Google Scholar · View at Scopus
  36. E. R. Kandel, I. Kupfermann, and S. Iversen, “Learning and memory,” in Principles of Neural Science, E. R. Kandel, J. H. Schwartz, and T. M. Jessell, Eds., McGraw-Hill, New York, NY, USA, 2000. View at Google Scholar
  37. M. M. Monaghan, J. S. Trimmer, and K. J. Rhodes, “Experimental localization of Kv1 family voltage-gated K+ channel α and β subunits in rat hippocampal formation,” Journal of Neuroscience, vol. 21, no. 16, pp. 5973–5983, 2001. View at Google Scholar · View at Scopus
  38. H. Wang, D. O. Kunkel, P. A. Schwartzkroin, and B. L. Tempel, “Localization of Kv1.1 and Kv1.2, two K+ channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain,” Journal of Neuroscience, vol. 14, no. 8, pp. 4588–4599, 1994. View at Google Scholar · View at Scopus
  39. K. H. Park, Y. H. Chung, C. M. Shin et al., “Immunohistochemical study on the distribution of the voltage-gated potassium channels in the gerbil hippocampus,” Neuroscience Letters, vol. 298, no. 1, pp. 29–32, 2001. View at Publisher · View at Google Scholar · View at Scopus
  40. C. B. Zhong, Y. P. Pan, X. Y. Tong, X. H. Xu, and X. L. Wang, “Delayed rectifier potassium currents and Kv2.1 mRNA increase in hippocampal neurons of scopolamine-induced memory-deficient rats,” Neuroscience Letters, vol. 373, no. 2, pp. 99–104, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. A. W. Varga, A. E. Anderson, J. P. Adams, H. Vogel, and J. D. Sweatt, “Input-specific immunolocalization of differentially phosphorylated Kv4.2 in the mouse brain,” Learning and Memory, vol. 7, no. 5, pp. 321–332, 2000. View at Publisher · View at Google Scholar · View at Scopus
  42. M. L. Tsaur, C. C. Chou, Y. H. Shih, and H. L. Wang, “Cloning, expression and CNS distribution of Kv4.3, an A-type K+ channel α subunit,” FEBS Letters, vol. 400, no. 2, pp. 215–220, 1997. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Martin, C. Lino de Oliveira, F. Mello de Queiroz, L. A. Pardo, W. Stühmer, and E. Del Bel, “Eag1 potassium channel immunohistochemistry in the CNS of adult rat and selected regions of human brain,” Neuroscience, vol. 155, no. 3, pp. 833–844, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. C. A. Sailer, W. A. Kaufmann, M. Kogler et al., “Immunolocalization of BK channels in hippocampal pyramidal neurons,” European Journal of Neuroscience, vol. 24, no. 2, pp. 442–454, 2006. View at Publisher · View at Google Scholar · View at Scopus
  45. G. Murer, C. Adelbrecht, I. Lauritzen et al., “An immunocytochemical study on the distribution of two G-protein-gated inward rectifier potassium channels (Girk2 and Girk4) in the adult rat brain,” Neuroscience, vol. 80, no. 2, pp. 345–357, 1997. View at Publisher · View at Google Scholar · View at Scopus
  46. K. Wickman, C. Karschin, A. Karschin, M. R. Picciotto, and D. E. Clapham, “Brain localization and behavioral impact of the G-protein-gated K+ channel subunit GIRK4,” Journal of Neuroscience, vol. 20, no. 15, pp. 5608–5615, 2000. View at Google Scholar · View at Scopus
  47. M. Iizuka, I. Tsunenari, Y. Momota, I. Akiba, and T. Kono, “Localization of a G-protein-coupled inwardly rectifying K+ channel, CIR, in the rat brain,” Neuroscience, vol. 77, no. 1, pp. 1–13, 1997. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Betourne, A. M. Bertholet, E. Labroue et al., “Involvement of hippocampal CA3 KATP channels in contextual memory,” Neuropharmacology, vol. 56, no. 3, pp. 615–625, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. C. Karschin, C. Ecke, F. M. Ashcroft, and A. Karschin, “Overlapping distribution of KATP channel-forming Kir6.2 subunit and the sulfonylurea receptor SUR1 in rodent brain,” FEBS Letters, vol. 401, no. 1, pp. 59–64, 1997. View at Publisher · View at Google Scholar · View at Scopus
  50. C. Ghelardini, N. Galeotti, and A. Bartolini, “Influence of potassium channel modulators on cognitive processes in mice,” British Journal of Pharmacology, vol. 123, no. 6, pp. 1079–1084, 1998. View at Publisher · View at Google Scholar · View at Scopus
  51. N. Meiri, C. Ghelardini, G. Tesco et al., “Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 9, pp. 4430–4434, 1997. View at Publisher · View at Google Scholar · View at Scopus
  52. A. Miyake, S. Takahashi, Y. Nakamura et al., “Disruption of the ether-à-go-go K+ channel gene BEC1/KCNH3 enhances cognitive function,” Journal of Neuroscience, vol. 29, no. 46, pp. 14637–14645, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. K. A. Vick, M. Guidi, and R. W. Stackman, “In vivo pharmacological manipulation of small conductance Ca2+-activated K+ channels influences motor behavior, object memory and fear conditioning,” Neuropharmacology, vol. 58, no. 3, pp. 650–659, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. E. A. Matthews and J. F. Disterhoft, “Blocking the BK channel impedes acquisition of trace eyeblink conditioning,” Learning and Memory, vol. 16, no. 2, pp. 106–109, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. R. S. Hammond, C. T. Bond, T. Strassmaier et al., “Small-conductance Ca2+-activated K+ channel type 2 (SK2) modulates hippocampal learning, memory, and synaptic plasticity,” Journal of Neuroscience, vol. 26, no. 6, pp. 1844–1853, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. R. W. Stackman Jr., C. T. Bond, and J. P. Adelman, “Contextual memory deficits observed in mice overexpressing small conductance Ca2+-activated K+ type 2 (KCa2.2, SK2) channels are caused by an encoding deficit,” Learning and Memory, vol. 15, no. 4, pp. 208–213, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. J. P. R. Jacobsen, J. P. Redrobe, H. H. Hansen et al., “Selective cognitive deficits and reduced hippocampal brain-derived neurotrophic factor mRNA expression in small-conductance calcium-activated K+ channel deficient mice,” Neuroscience, vol. 163, no. 1, pp. 73–81, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. P. Y. Deng, Z. Xiao, C. Yang et al., “GABAB receptor activation inhibits neuronal excitability and spatial learning in the entorhinal cortex by activating TREK-2 K+ channels,” Neuron, vol. 63, no. 2, pp. 230–243, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Kourrich, C. Manrique, P. Salin, and C. Mourre, “Transient hippocampal down-regulation of Kv1.1 subunit mRNA during associative learning in rats,” Learning and Memory, vol. 12, no. 5, pp. 511–519, 2005. View at Publisher · View at Google Scholar · View at Scopus
  60. B. Engeland, A. Neu, J. Ludwig, J. Roeper, and O. Pongs, “Cloning and functional expression of rat ether-a-go-go-like K+ channel genes,” Journal of Physiology, vol. 513, no. 3, pp. 647–654, 1998. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Miyake, S. Mochizuki, H. Yokoi, M. Kohda, and K. Furuichi, “New ether-a-go-go K+ channel family members localized in human telencephalon,” Journal of Biological Chemistry, vol. 274, no. 35, pp. 25018–25025, 1999. View at Publisher · View at Google Scholar · View at Scopus
  62. G. Gimenez-Gallego, M. A. Navia, J. P. Reuben, G. M. Katz, G. J. Kaczorowski, and M. L. Garcia, “Purification, sequence, and model structure of charybdotoxin, a potent selective inhibitor of calcium-activated potassium channels,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 10, pp. 3329–3333, 1988. View at Google Scholar · View at Scopus
  63. W. Jin and Z. Lu, “A novel high-affinity inhibitor for inward-rectifier K+ channels,” Biochemistry, vol. 37, no. 38, pp. 13291–13299, 1998. View at Publisher · View at Google Scholar · View at Scopus
  64. L. Marvin, E. De, P. Cosette, J. Gagnon, G. Molle, and C. Lange, “Isolation, amino acid sequence and functional assays of SGTx1. The first toxin purified from the venom of the spider Scodra griseipes,” European Journal of Biochemistry, vol. 265, no. 2, pp. 572–579, 1999. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Nolting, T. Ferraro, D. D'Hoedt, and M. Stocker, “An amino acid outside the pore region influences apamin sensitivity in small conductance Ca2+-activated K+ channels,” Journal of Biological Chemistry, vol. 282, no. 6, pp. 3478–3486, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. C. Lamy, S. J. Goodchild, K. L. Weatherall et al., “Allosteric block of KCa2 channels by apamin,” Journal of Biological Chemistry, vol. 285, no. 35, pp. 27067–27077, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. B. Jouirou, S. Mouhat, N. Andreotti, M. De Waard, and J. M. Sabatier, “Toxin determinants required for interaction with voltage-gated K+ channels,” Toxicon, vol. 43, no. 8, pp. 909–914, 2004. View at Publisher · View at Google Scholar · View at Scopus
  68. S. Mouhat, B. Jouirou, A. Mosbah, M. De Waard, and J. M. Sabatier, “Diversity of folds in animal toxins acting on ion channels,” Biochemical Journal, vol. 378, no. 3, pp. 717–726, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. S. Mouhat, N. Andreotti, B. Jouriou, and J. M. Sabatier, “Animal toxins acting on voltage-gated potassium channels,” Current Pharmaceutical Design, vol. 14, no. 24, pp. 2503–2518, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Dauplais, A. Lecoq, J. Song et al., “On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures,” Journal of Biological Chemistry, vol. 272, no. 7, pp. 4302–4309, 1997. View at Publisher · View at Google Scholar · View at Scopus
  71. G. B. Gurrola, B. Rosati, M. Rocchetti et al., “A toxin to nervous, cardiac, and endocrine ERG K+ channels isolated from Centruroides noxius scorpion venom,” FASEB Journal, vol. 13, no. 8, pp. 953–962, 1999. View at Google Scholar · View at Scopus
  72. Y. V. Korolkova, S. A. Kozlov, A. V. Lipkin et al., “An ERG Channel Inhibitor from the Scorpion Buthus eupeus,” Journal of Biological Chemistry, vol. 276, no. 13, pp. 9868–9876, 2001. View at Publisher · View at Google Scholar · View at Scopus
  73. P. Escoubas, C. Bernard, G. Lambeau, M. Lazdunski, and H. Darbon, “Recombinant production and solution structure of PcTx1, the specific peptide inhibitor of ASIC1a proton-gated cation channels,” Protein Science, vol. 12, no. 7, pp. 1332–1343, 2003. View at Publisher · View at Google Scholar · View at Scopus
  74. Z. Lu and R. MacKinnon, “Purification, characterization, and synthesis of an inward-rectifier K+ channel inhibitor from scorpion venom,” Biochemistry, vol. 36, no. 23, pp. 6936–6940, 1997. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Tytgat, K. G. Chandy, M. L. Garcia et al., “A unified nomenclature for short-chain peptides isolated from scorpion venoms: α-KTx molecular subfamilies,” Trends in Pharmacological Sciences, vol. 20, no. 11, pp. 444–447, 1999. View at Publisher · View at Google Scholar · View at Scopus
  76. K. N. Srinivasan, V. Sivaraja, I. Huys et al., “kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity,” Journal of Biological Chemistry, vol. 277, no. 33, pp. 30040–30047, 2002. View at Google Scholar · View at Scopus
  77. B. Chagot, C. Pimentel, L. Dai et al., “An unusual fold for potassium channel blockers: NMR structure of three toxins from the scorpion Opisthacanthus madagascariensis,” Biochemical Journal, vol. 388, no. 1, pp. 263–271, 2005. View at Publisher · View at Google Scholar · View at Scopus
  78. T. S. Camargos, R. Restano-Cassulini, L. D. Possani et al., “The new kappa-KTx 2.5 from the scorpion Opisthacanthus cayaporum,” Peptides, vol. 32, no. 7, pp. 1509–1517, 2011. View at Publisher · View at Google Scholar
  79. R. C. Rodríguez De La Vega and L. D. Possani, “Current views on scorpion toxins specific for K+-channels,” Toxicon, vol. 43, no. 8, pp. 865–875, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. G. Estrada, E. Villegas, and G. Corzo, “Spider venoms: a rich source of acylpolyamines and peptides as new leads for CNS drugs,” Natural Product Reports, vol. 24, no. 1, pp. 145–161, 2007. View at Publisher · View at Google Scholar · View at Scopus
  81. K. J. Swartz, “Tarantula toxins interacting with voltage sensors in potassium channels,” Toxicon, vol. 49, no. 2, pp. 213–230, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. K. J. Swartz and R. MacKinnon, “Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites,” Neuron, vol. 18, no. 4, pp. 665–673, 1997. View at Google Scholar · View at Scopus
  83. H. C. Lee, J. M. Wang, and K. J. Swartz, “Interaction between extracellular hanatoxin and the resting conformation of the voltage-sensor paddle in Kv channels,” Neuron, vol. 40, no. 3, pp. 527–536, 2003. View at Publisher · View at Google Scholar · View at Scopus
  84. S. Y. Lee and R. MacKinnon, “A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom,” Nature, vol. 430, no. 6996, pp. 232–235, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. L. R. Phillips, M. Milescu, Y. Li-Smerin, J. A. Mindell, J. I. Kim, and K. J. Swartz, “Voltage-sensor activation with a tarantula toxin as cargo,” Nature, vol. 436, no. 7052, pp. 857–860, 2005. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Milescu, J. Vobecky, S. H. Roh et al., “Tarantula toxins interact with voltage sensors within lipid membranes,” Journal of General Physiology, vol. 130, no. 5, pp. 497–511, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. H. Raghuraman and A. Chattopadhyay, “Melittin: a membrane-active peptide with diverse functions,” Bioscience Reports, vol. 27, no. 4-5, pp. 189–223, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. E. Habermann, “Apamin,” Pharmacology and Therapeutics, vol. 25, no. 2, pp. 255–270, 1984. View at Google Scholar · View at Scopus
  89. X. Xu and J. W. Nelson, “Solution structure of tertiapin determined using nuclear magnetic resonance and distance geometry,” Proteins: Structure, Function and Genetics, vol. 17, no. 2, pp. 124–137, 1993. View at Publisher · View at Google Scholar · View at Scopus
  90. E. M. Dotimas, K. R. Hamid, R. C. Hider, and U. Ragnarsson, “Isolation and structure analysis of bee venom mast cell degranulating peptide,” Biochimica et Biophysica Acta, vol. 911, no. 3, pp. 285–293, 1987. View at Google Scholar · View at Scopus
  91. K. L. Weatherall, S. J. Goodchild, D. E. Jane, and N. V. Marrion, “Small conductance calcium-activated potassium channels: from structure to function,” Progress in Neurobiology, vol. 91, no. 3, pp. 242–255, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. S. Kourrich, C. Mourre, and B. Soumireu-Mourat, “Kaliotoxin, a Kv1.1 and Kv1.3 channel blocker, improves associative learning in rats,” Behavioural Brain Research, vol. 120, no. 1, pp. 35–46, 2001. View at Publisher · View at Google Scholar · View at Scopus
  93. T. M. Edwards and N. S. Rickard, “Pharmaco-behavioural evidence indicating a complex role for ryanodine receptor calcium release channels in memory processing for a passive avoidance task,” Neurobiology of Learning and Memory, vol. 86, no. 1, pp. 1–8, 2006. View at Publisher · View at Google Scholar · View at Scopus
  94. C. Messier, C. Mourre, B. Bontempi, J. Sif, M. Lazdunski, and C. Destrade, “Effect of apamin, a toxin that inhibits Ca2+-dependent K+ channels, on learning and memory processes,” Brain Research, vol. 551, no. 1-2, pp. 322–326, 1991. View at Google Scholar · View at Scopus
  95. O. Deschaux, J. C. Bizot, and M. Goyffon, “Apamin improves learning in an object recognition task in rats,” Neuroscience Letters, vol. 222, no. 3, pp. 159–162, 1997. View at Publisher · View at Google Scholar · View at Scopus
  96. O. Deschaux and J. C. Bizot, “Effect of apamin, a selective blocker of Ca2+-activated K+-channel, on habituation and passive avoidance responses in rats,” Neuroscience Letters, vol. 227, no. 1, pp. 57–60, 1997. View at Publisher · View at Google Scholar · View at Scopus
  97. S. Ikonen, B. Schmidt, and P. Riekkinen, “Apamin improves spatial navigation in medial septal-lesioned mice,” European Journal of Pharmacology, vol. 347, no. 1, pp. 13–21, 1998. View at Publisher · View at Google Scholar · View at Scopus
  98. F. J. Van Der Staay, R. J. Fanelli, A. Blokland, and B. H. Schmidt, “Behavioral effects of apamin, a selective inhibitor of the SKCa-channel, in mice and rats,” Neuroscience and Biobehavioral Reviews, vol. 23, no. 8, pp. 1087–1110, 1999. View at Publisher · View at Google Scholar · View at Scopus
  99. S. Ikonen and P. Riekkinen, “Effects of apamin on memory processing of hippocampal-lesioned mice,” European Journal of Pharmacology, vol. 382, no. 3, pp. 151–156, 1999. View at Publisher · View at Google Scholar · View at Scopus
  100. C. Fournier, S. Kourrich, B. Soumireu-Mourat, and C. Mourre, “Apamin improves reference memory but not procedural memory in rats by blocking small conductance Ca2+-activated K+ channels in an olfactory discrimination task,” Behavioural Brain Research, vol. 121, no. 1-2, pp. 81–93, 2001. View at Publisher · View at Google Scholar · View at Scopus
  101. B. Mpari, I. Regaya, G. Escoffier, and C. Mourre, “Differential effects of two blockers of small conductance Ca2+-activated K+ channels, apamin and lei-Dab7, on learning and memory in rats,” Journal of integrative neuroscience., vol. 4, no. 3, pp. 381–396, 2005. View at Google Scholar · View at Scopus
  102. A. R. Brennan, B. Dolinsky, M. A. T. Vu, M. Stanley, M. F. Yeckel, and A. F. T. Arnsten, “Blockade of IP3-mediated SK channel signaling in the rat medial prefrontal cortex improves spatial working memory,” Learning and Memory, vol. 15, no. 3, pp. 93–96, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. K. D. Baker, T. M. Edwards, and N. S. Rickard, “Blocking SK channels impairs long-term memory formation in young chicks,” Behavioural Brain Research, vol. 216, no. 1, pp. 458–462, 2011. View at Publisher · View at Google Scholar · View at Scopus
  104. P. Haux, H. Sawerthal, and E. Habermann, “Sequence analysis of bee venom neurotoxin (apamine) from its tryptic and chymotryptic cleavage products,” Hoppe-Seyler's Zeitschrift fur Physiologische Chemie, vol. 348, no. 6, pp. 737–738, 1967. View at Google Scholar · View at Scopus
  105. E. Habermann, “Bee and wasp venoms,” Science, vol. 177, no. 4046, pp. 314–322, 1972. View at Google Scholar · View at Scopus
  106. G. L. Callewaert, R. Shipolini, and C. A. Vernon, “The disulphide bridges of apamin,” FEBS Letters, vol. 1, no. 2, pp. 111–113, 1968. View at Google Scholar · View at Scopus
  107. J. P. Vincent, H. Schweitz, and M. Lazdunski, “Structure-function relationships and site of action of apamin, a neurotoxic polypeptide of bee venom with an action on the central nervous system,” Biochemistry, vol. 14, no. 11, pp. 2521–2525, 1975. View at Google Scholar · View at Scopus
  108. E. Habermann and D. Cheng Raude, “Central neurotoxicity of apamin, crotamin, phospholipase A and α amanitin,” Toxicon, vol. 13, no. 6, pp. 465–473, 1975. View at Google Scholar · View at Scopus
  109. M. L. Garcia, A. Galvez, M. Garcia-Calvo, V. F. King, J. Vazquez, and G. J. Kaczorowski, “Use of toxins to study potassium channels,” Journal of Bioenergetics and Biomembranes, vol. 23, no. 4, pp. 615–646, 1991. View at Google Scholar · View at Scopus
  110. C. Heurteaux, C. Messier, C. Destrade, and M. Lazdunski, “Memory processing and apamin induce immediately early gene expression in mouse brain,” Molecular Brain Research, vol. 18, no. 1-2, pp. 17–22, 1993. View at Google Scholar · View at Scopus
  111. V. G. Shakkottai, I. Regaya, H. Wulff et al., “Design and characterization of a highly selective peptide inhibitor of the small conductance calcium-activated K+ channel, SKCa2,” Journal of Biological Chemistry, vol. 276, no. 46, pp. 43145–43151, 2001. View at Publisher · View at Google Scholar · View at Scopus
  112. S. I. Yamada, H. Takechi, I. Kanchiku, T. Kita, and N. Kato, “Small-conductance Ca2+-dependent K+ channels are the target of spike-induced Ca2+ release in a feedback regulation of pyramidal cell excitability,” Journal of Neurophysiology, vol. 91, no. 5, pp. 2322–2329, 2004. View at Publisher · View at Google Scholar · View at Scopus
  113. A. T. Gulledge, S. B. Park, Y. Kawaguchi, and G. J. Stuart, “Heterogeneity of phasic cholinergic signaling in neocortical neurons,” Journal of Neurophysiology, vol. 97, no. 3, pp. 2215–2229, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. A. M. Hagenston, J. S. Fitzpatrick, and M. F. Yeckel, “MGluR-mediated calcium waves that invade the soma regulate firing in layer V medial prefrontal cortical pyramidal neurons,” Cerebral Cortex, vol. 18, no. 2, pp. 407–423, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. E. S. L. Faber and P. Sah, “Functions of SK channels in central neurons,” Clinical and Experimental Pharmacology and Physiology, vol. 34, no. 10, pp. 1077–1083, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. E. S. L. Faber, “Functional interplay between NMDA receptors, SK channels and voltage-gated Ca2+ channels regulates synaptic excitability in the medial prefrontal cortex,” Journal of Physiology, vol. 588, no. 8, pp. 1281–1292, 2010. View at Publisher · View at Google Scholar · View at Scopus
  117. C. Miller, E. Moczydlowski, R. Latorre, and M. Phillips, “Charybdotoxin a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle,” Nature, vol. 313, no. 6000, pp. 316–318, 1985. View at Google Scholar · View at Scopus
  118. D. R. Gehlert and S. L. Gackenheimer, “Comparison of the distribution of binding sites for the potassium channel ligands [125I]apamin, [125I]charybdotoxin and [125I]iodoglyburide in the rat brain,” Neuroscience, vol. 52, no. 1, pp. 191–205, 1993. View at Publisher · View at Google Scholar · View at Scopus
  119. S. M. Cochran, A. L. Harvey, and J. A. Pratt, “Regionally selective alterations in local cerebral glucose utilization evoked by charybdotoxin, a blocker of central voltage-activated K+-channels,” European Journal of Neuroscience, vol. 14, no. 9, pp. 1455–1463, 2001. View at Publisher · View at Google Scholar · View at Scopus
  120. M. Crest, G. Jacquet, M. Gola et al., “Kaliotoxin, a novel peptidyl inhibitor of neuronal BK-type Ca2+-activated K+ channels characterized from Androctonus mauretanicus mauretanicus venom,” Journal of Biological Chemistry, vol. 267, no. 3, pp. 1640–1647, 1992. View at Google Scholar · View at Scopus
  121. A. Galvez, G. Gimenez-Gallego, J. P. Reuben et al., “Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus,” Journal of Biological Chemistry, vol. 265, no. 19, pp. 11083–11090, 1990. View at Google Scholar · View at Scopus
  122. K. M. Giangiacomo, M. L. Garcia, and O. B. McManus, “Mechanism of iberiotoxin block of the large-conductance calcium-activated potassium channel from bovine aortic smooth muscle,” Biochemistry, vol. 31, no. 29, pp. 6719–6727, 1992. View at Google Scholar · View at Scopus
  123. L. R. Shao, R. Halvorsrud, L. Borg-Graham, and J. F. Storm, “The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells,” Journal of Physiology, vol. 521, no. 1, pp. 135–146, 1999. View at Google Scholar · View at Scopus
  124. B. G. Schreurs, P. A. Gusev, D. Tomsic, D. L. Alkon, and T. Shi, “Intracellular correlates of acquisition and long-term memory of classical conditioning in Purkinje cell dendrites in slices of rabbit cerebellar lobule HVI,” Journal of Neuroscience, vol. 18, no. 14, pp. 5498–5507, 1998. View at Google Scholar · View at Scopus
  125. T. Himi, H. Saito, and T. Nakajima, “Spider toxin (JSTX-3) inhibits the memory retrieval of passive avoidance tests,” Journal of Neural Transmission. General Section, vol. 80, no. 1, pp. 79–89, 1990. View at Publisher · View at Google Scholar · View at Scopus
  126. A. Vincent, C. Buckley, J. M. Schott et al., “Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis,” Brain, vol. 127, no. 3, pp. 701–712, 2004. View at Publisher · View at Google Scholar · View at Scopus
  127. N. E. Anderson and P. A. Barber, “Limbic encephalitis—a review,” Journal of Clinical Neuroscience, vol. 15, no. 9, pp. 961–971, 2008. View at Publisher · View at Google Scholar · View at Scopus
  128. C. Buckley, J. Oger, L. Clover et al., “Potassium channel antibodies in two patients with reversible limbic encephalitis,” Annals of Neurology, vol. 50, no. 1, pp. 73–78, 2001. View at Publisher · View at Google Scholar · View at Scopus
  129. T. Harrower, T. Foltynie, L. Kartsounis, R. N. De Silva, and J. R. Hodges, “A case of voltage-gated potassium channel antibody-related limbic encephalitis,” Nature Clinical Practice Neurology, vol. 2, no. 6, pp. 339–343, 2006. View at Publisher · View at Google Scholar · View at Scopus
  130. L. D. Kartsounis and R. de Silva, “Unusual amnesia in a patient with VGKC-Ab limbic encephalitis: a case study,” Cortex, vol. 47, no. 4, pp. 451–459, 2011. View at Publisher · View at Google Scholar · View at Scopus
  131. M. Kaul, J. Zheng, S. Okamoto, H. E. Gendelman, and S. A. Lipton, “HIV-1 infection and AIDS: consequences for the central nervous system,” Cell Death and Differentiation, vol. 12, no. 1, pp. 878–892, 2005. View at Publisher · View at Google Scholar · View at Scopus
  132. K. A. Lindl, D. R. Marks, D. L. Kolson, and K. L. Jordan-Sciutto, “HIV-associated neurocognitive disorder: pathogenesis and therapeutic opportunities,” Journal of Neuroimmune Pharmacology, vol. 5, no. 3, pp. 294–309, 2010. View at Publisher · View at Google Scholar · View at Scopus
  133. J. P. Keblesh, B. C. Reiner, J. Liu, and H. Xiong, “Pathogenesis of human immunodeficiency virus type-1 (HIV-1)-associated dementia: role of voltage-gated potassium channels,” Retrovirology, vol. 2, pp. 1–10, 2008. View at Google Scholar
  134. J. Keblesh, D. Hu, and H. Xiong, “Voltage-gated potassium channels in human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorders,” Journal of Neuroimmune Pharmacology, vol. 4, no. 1, pp. 60–70, 2009. View at Publisher · View at Google Scholar · View at Scopus
  135. B. B. Gelman, V. M. Soukup, K. W. Schuenke et al., “Acquired neuronal channelopathies in HIV-associated dementia,” Journal of Neuroimmunology, vol. 157, no. 1-2, pp. 111–119, 2004. View at Publisher · View at Google Scholar · View at Scopus
  136. W. E. Zink, E. Anderson, J. Boyle et al., “Impaired spatial cognition and synaptic potentiation in a murine model of human immunodeficiency virus type 1 encephalitis,” Journal of Neuroscience, vol. 22, no. 6, pp. 2096–2105, 2002. View at Google Scholar · View at Scopus
  137. E. R. Anderson, J. Boyle, W. E. Zink, Y. Persidsky, H. E. Gendelman, and H. Xiong, “Hippocampal synaptic dysfunction in a murine model of human immunodeficiency virus type 1 encephalitis,” Neuroscience, vol. 118, no. 2, pp. 359–369, 2003. View at Publisher · View at Google Scholar · View at Scopus
  138. J. P. Keblesh, H. Dou, H. E. Gendelman, and H. Xiong, “4-aminopyridine improves spatial memory in a murine model of HIV-1 encephalitis,” Journal of Neuroimmune Pharmacology, vol. 4, no. 3, pp. 317–327, 2009. View at Publisher · View at Google Scholar · View at Scopus
  139. S. A. Stilo and R. M. Murray, “The epidemiology of schizophrenia: replacing dogma with knowledge,” Dialogues in Clinical Neuroscience, vol. 12, no. 3, pp. 305–315, 2010. View at Google Scholar · View at Scopus
  140. S. R. Kay, A. Fiszbein, and L. A. Opler, “The positive and negative syndrome scale (PANSS) for schizophrenia,” Schizophrenia Bulletin, vol. 13, no. 2, pp. 261–276, 1987. View at Google Scholar · View at Scopus
  141. R. W. Heinrichs, “The primacy of cognition in schizophrenia,” American Psychologist, vol. 60, no. 3, pp. 229–242, 2005. View at Publisher · View at Google Scholar · View at Scopus
  142. T. W. Weickert, T. E. Goldberg, J. M. Gold, L. B. Bigelow, M. F. Egan, and D. R. Weinberger, “Cognitive impairments in patients with schizophrenia displaying preserved and compromised intellect,” Archives of General Psychiatry, vol. 57, no. 9, pp. 907–913, 2000. View at Google Scholar · View at Scopus
  143. A. I. Potter and P. G. Nestor, “IQ subtypes in schizophrenia: distinct symptom and neuropsychological profiles,” Journal of Nervous and Mental Disease, vol. 198, no. 8, pp. 580–585, 2010. View at Publisher · View at Google Scholar · View at Scopus
  144. B. K. Lipska and D. R. Weinberger, “To model a psychiatric disorder in animals: schizophrenia as a reality test,” Neuropsychopharmacology, vol. 23, no. 3, pp. 223–239, 2000. View at Publisher · View at Google Scholar · View at Scopus
  145. M. N. Quan, Y. T. Tian, K. H. Xu, T. Zhang, and Z. Yang, “Post weaning social isolation influences spatial cognition, prefrontal cortical synaptic plasticity and hippocampal potassium ion channels in Wistar rats,” Neuroscience, vol. 169, no. 1, pp. 214–222, 2010. View at Publisher · View at Google Scholar · View at Scopus
  146. X. Chen, L. L. Yuan, C. Zhao et al., “Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons,” Journal of Neuroscience, vol. 26, no. 47, pp. 12143–12151, 2006. View at Publisher · View at Google Scholar · View at Scopus
  147. M. L. Bourdeau, F. Morin, C. E. Laurent, M. Azzi, and J. C. Lacaille, “Kv4.3-mediated A-type K+ currents underlie rhythmic activity in hippocampal interneurons,” Journal of Neuroscience, vol. 27, no. 8, pp. 1942–1953, 2007. View at Publisher · View at Google Scholar · View at Scopus
  148. M. Gallagher and M. T. Koh, “Episodic memory on the path to Alzheimer's disease,” Current Opinion in Neurobiology, vol. 21, no. 6, pp. 929–934, 2011. View at Publisher · View at Google Scholar
  149. J. J. Dougherty, J. Wu, and R. A. Nichols, “β-amyloid regulation of presynaptic nicotinic receptors in rat hippocampus and neocortex,” Journal of Neuroscience, vol. 23, no. 17, pp. 6740–6747, 2003. View at Google Scholar · View at Scopus
  150. L. Betancourt and L. V. Colom, “Potassium (K+) channel expression in basal forebrain cholinergic neurons,” Journal of Neuroscience Research, vol. 61, no. 6, pp. 646–651, 2000. View at Publisher · View at Google Scholar · View at Scopus
  151. J. F. Kidd and D. B. Sattelle, “The effects of amyloid peptides on A-type K+ currents of Drosophila larval cholinergic neurons: modeled actions on firing properties,” Invertebrate Neuroscience, vol. 6, no. 4, pp. 207–213, 2006. View at Publisher · View at Google Scholar · View at Scopus
  152. J. F. Kidd, L. A. Brown, and D. B. Sattelle, “Effects of amyloid peptides on A-type K+ currents of Drosophila larval cholinergic neurons,” Journal of Neurobiology, vol. 66, no. 5, pp. 476–487, 2006. View at Publisher · View at Google Scholar · View at Scopus
  153. N. Demaurex and G. L. Petheö, “Electron and proton transport by NADPH oxidases,” Philosophical Transactions of the Royal Society B, vol. 360, no. 1464, pp. 2315–2325, 2005. View at Publisher · View at Google Scholar
  154. M. L. Block, L. Zecca, and J. S. Hong, “Microglia-mediated neurotoxicity: uncovering the molecular mechanisms,” Nature Reviews Neuroscience, vol. 8, no. 1, pp. 57–69, 2007. View at Publisher · View at Google Scholar · View at Scopus
  155. R. Khanna, L. Roy, X. Zhu, and L. C. Schlichter, “K+ channels and the microglial respiratory burst,” American Journal of Physiology, vol. 280, no. 4, pp. C796–C806, 2001. View at Google Scholar · View at Scopus
  156. C. B. Fordyce, R. Jagasia, X. Zhu, and L. C. Schlichter, “Microglia Kv1.3 channels contribute to their ability to kill neurons,” Journal of Neuroscience, vol. 25, no. 31, pp. 7139–7149, 2005. View at Publisher · View at Google Scholar · View at Scopus
  157. A. Compston and A. Coles, “Multiple sclerosis,” The Lancet, vol. 372, no. 9648, pp. 1502–1517, 2008. View at Publisher · View at Google Scholar · View at Scopus
  158. N. D. Chiaravalloti and J. DeLuca, “Cognitive impairment in multiple sclerosis,” The Lancet Neurology, vol. 7, no. 12, pp. 1139–1151, 2008. View at Publisher · View at Google Scholar · View at Scopus
  159. L. Gutmann and L. Gutmann, “Axonal channelopathies: an evolving concept in the pathogenesis of peripheral nerve disorders,” Neurology, vol. 47, no. 1, pp. 18–21, 1996. View at Google Scholar · View at Scopus
  160. H. Wang, D. D. Kunkel, T. M. Martin, P. A. Schwartzkroin, and B. L. Tempel, “Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons,” Nature, vol. 365, no. 6441, pp. 75–79, 1993. View at Publisher · View at Google Scholar · View at Scopus
  161. E. Jankowska, A. Lundberg, P. Rudomin, and E. Sykova, “Effects of 4-aminopyridine on transmission in excitatory and inhibitory synapses in the spinal cord,” Brain Research, vol. 136, no. 2, pp. 387–392, 1977. View at Publisher · View at Google Scholar · View at Scopus
  162. R. M. Sherratt, H. Bostock, and T. A. Sears, “Effects of 4-aminopyridine on normal and demyelinated mammalian nerve fibres,” Nature, vol. 283, no. 5747, pp. 570–572, 1980. View at Google Scholar · View at Scopus
  163. E. F. Targ and J. D. Kocsis, “4-Aminopyridine leads to restoration of conduction in demyelinated rat sciatic nerve,” Brain Research, vol. 328, no. 2, pp. 358–361, 1985. View at Publisher · View at Google Scholar · View at Scopus
  164. K. J. Smith, P. A. Felts, and G. R. John, “Effects of 4-aminopyridine on demyelinated axons, synapses and muscle tension,” Brain, vol. 123, no. 1, pp. 171–184, 2000. View at Google Scholar · View at Scopus
  165. C. T. Bever Jr., “The current status of studies of aminopyridines in patients with multiple sclerosis,” Annals of Neurology, vol. 36, pp. S118–S121, 1994. View at Publisher · View at Google Scholar · View at Scopus
  166. C. H. Polman, F. W. Bertelsmann, A. C. Van Loenen, and J. C. Koetsier, “4-Aminopyridine in the treatment of patients with multiple sclerosis: long-term efficacy and safety,” Archives of Neurology, vol. 51, no. 3, pp. 292–296, 1994. View at Google Scholar · View at Scopus
  167. J. Holoshitz, Y. Naparstek, and A. Ben-Nun, “T lymphocyte lines induce autoimmune encephalomyelitis, delayed hypersensitivity and bystander encephalitis,” European Journal of Immunology, vol. 14, no. 8, pp. 729–734, 1984. View at Google Scholar
  168. C. Beeton, H. Wulff, J. Barbaria et al., “Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 24, pp. 13942–13947, 2001. View at Publisher · View at Google Scholar · View at Scopus
  169. C. M. Fanger, H. Rauer, A. L. Neben et al., “Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels,” Journal of Biological Chemistry, vol. 276, no. 15, pp. 12249–12256, 2001. View at Publisher · View at Google Scholar · View at Scopus
  170. C. Beeton, J. Barbaria, P. Giraud et al., “Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation,” Journal of Immunology, vol. 166, no. 2, pp. 936–944, 2001. View at Google Scholar · View at Scopus
  171. A. Solari, B. Uitdehaag, G. Giuliani, E. Pucci, and C. Taus, “Aminopyridines for symptomatic treatment in multiple sclerosis,” Cochrane Database of Systematic Reviews, no. 4, Article ID CD001330, 2001. View at Google Scholar
  172. A. R. Korenke, M. P. Rivey, and D. R. Allington, “Sustained-release fampridine for symptomatic treatment of multiple sclerosis,” Annals of Pharmacotherapy, vol. 42, no. 10, pp. 1458–1465, 2008. View at Publisher · View at Google Scholar · View at Scopus
  173. “Medication guide for Ampyra,” http://www.fda.gov/downloads/Drugs/DrugSafety/UCM199168.pdf.
  174. W. R. G. Gibb, “Neuropathology of Parkinson's disease and related syndromes,” Neurologic Clinics, vol. 10, no. 2, pp. 361–376, 1992. View at Google Scholar · View at Scopus
  175. J. Jankovic, “Parkinson's disease: clinical features and diagnosis,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 79, no. 4, pp. 368–376, 2008. View at Publisher · View at Google Scholar · View at Scopus
  176. B. Liss, O. Haeckel, J. Wildmann, T. Miki, S. Seino, and J. Roeper, “K-ATP channels promote the differential degeneration of dopaminergic midbrain neurons,” Nature Neuroscience, vol. 8, no. 12, pp. 1742–1751, 2005. View at Publisher · View at Google Scholar · View at Scopus
  177. B. Liss and J. Roeper, “ATP-sensitive potassium channels in dopaminergic neurons: transducers of mitochondrial dysfunction,” News in Physiological Sciences, vol. 16, no. 5, pp. 214–217, 2001. View at Google Scholar · View at Scopus
  178. A. H. V. Schapira, M. Gu, J. W. Taanman et al., “Mitochondria in the etiology and pathogenesis of Parkinson's disease,” Annals of Neurology, vol. 44, no. 3, pp. S89–S98, 1998. View at Google Scholar · View at Scopus
  179. N. Patil, D. R. Cox, D. Bhat, M. Faham, R. M. Myers, and A. S. Peterson, “A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation,” Nature Genetics, vol. 11, no. 2, pp. 126–129, 1995. View at Publisher · View at Google Scholar · View at Scopus
  180. G. Tunnicliff, “Basis of the antiseizure action of phenytoin,” General Pharmacology, vol. 27, no. 7, pp. 1091–1097, 1996. View at Publisher · View at Google Scholar · View at Scopus
  181. W. Löscher, “New visions in the pharmacology of anticonvulsion,” European Journal of Pharmacology, vol. 342, no. 1, pp. 1–13, 1998. View at Publisher · View at Google Scholar · View at Scopus
  182. D. E. Blum, “New drugs for persons with epilepsy,” Advances in neurology, vol. 76, pp. 57–87, 1998. View at Google Scholar · View at Scopus
  183. R. Guerrini, “Epilepsy in children,” Lancet, vol. 367, no. 9509, pp. 499–524, 2006. View at Publisher · View at Google Scholar · View at Scopus
  184. A. Aldenkamp and J. Arends, “The relative influence of epileptic EEG discharges, short nonconvulsive seizures, and type of epilepsy on cognitive function,” Epilepsia, vol. 45, no. 1, pp. 54–63, 2004. View at Publisher · View at Google Scholar · View at Scopus
  185. C. B. Dodrill, “Neuropsychological effects of seizures,” Epilepsy and Behavior, vol. 5, no. 1, pp. S21–S24, 2004. View at Publisher · View at Google Scholar · View at Scopus
  186. E. Beghi, G. De Maria, G. Gobbi, and E. Veneselli, “Diagnosis and treatment of the first epileptic seizure: guidelines of the Italian League against Epilepsy,” Epilepsia, vol. 47, no. 5, pp. 2–8, 2006. View at Publisher · View at Google Scholar · View at Scopus
  187. K. J. Meador, “Cognitive and memory effects of the new antiepileptic drugs,” Epilepsy Research, vol. 68, no. 1, pp. 63–67, 2006. View at Publisher · View at Google Scholar · View at Scopus
  188. B. Hermann, “Cognition in epilepsy and its transient impairment,” Epilepsy and Behavior, vol. 22, no. 3, p. 419, 2011. View at Publisher · View at Google Scholar
  189. P. N'Gouemo, “Targeting BK (big potassium) channels in epilepsy,” Expert Opinion on Therapeutic Targets, vol. 15, no. 11, pp. 1283–1295, 2011. View at Publisher · View at Google Scholar
  190. B. S. Meldrum, “Identification and preclinical testing of novel antiepileptic compounds,” Epilepsia, vol. 38, no. 9, pp. S7–S15, 1997. View at Google Scholar · View at Scopus
  191. B. Milner, “Disorders of learning and memory after temporal lobe lesions in man,” Clinical neurosurgery, vol. 19, pp. 421–446, 1972. View at Google Scholar · View at Scopus
  192. B. P. Hermann, M. Seidenberg, J. Schoenfeld, and K. Davies, “Neuropsychological characteristics of the syndrome of mesial temporal lobe epilepsy,” Archives of Neurology, vol. 54, no. 4, pp. 369–376, 1997. View at Google Scholar · View at Scopus
  193. H.-G. Wieser, “Mesial temporal lobe epilepsy with hippocampal sclerosis,” Epilepsia, vol. 45, no. 6, pp. 695–714, 2004. View at Publisher · View at Google Scholar
  194. M. M. Saling, “Verbal memory in mesial temporal lobe epilepsy: beyond material specificity,” Brain, vol. 132, no. 3, pp. 570–582, 2009. View at Publisher · View at Google Scholar · View at Scopus
  195. E. C. Cooper, “Potassium channels: how genetic studies of epileptic syndromes open paths to new therapeutic targets and drugs,” Epilepsia, vol. 42, no. 5, pp. 49–54, 2001. View at Google Scholar · View at Scopus
  196. B. S. Meldrum and M. A. Rogawski, “Molecular targets for antiepileptic drug development,” Neurotherapeutics, vol. 4, no. 1, pp. 18–61, 2007. View at Publisher · View at Google Scholar · View at Scopus
  197. C. E. Stafstrom, S. Grippon, and P. Kirkpatrick, “Ezogabine (retigabine),” Nature Reviews Drug Discovery, vol. 10, no. 10, pp. 729–730, 2011. View at Publisher · View at Google Scholar
  198. H. Vacher, G. Prestipino, M. Crest, and M. F. Martin-Eauclaire, “Definition of the alpha-KTx15 subfamily,” Toxicon, vol. 43, no. 8, pp. 887–894, 2004. View at Publisher · View at Google Scholar · View at Scopus
  199. W. J. Song, T. Tkatch, G. Baranauskas, N. Ichinohe, S. T. Kitai, and D. J. Surmeier, “Somatodendritic depolarization-activated potassium currents in rat neostriatal cholinergic interneurons are predominantly of the a type and attributable to coexpression of Kv4.2 and Kv4.1 subunits,” Journal of Neuroscience, vol. 18, no. 9, pp. 3124–3137, 1998. View at Google Scholar · View at Scopus
  200. D. Guan, T. Tkatch, D. J. Surmeier, W. E. Armstrong, and R. C. Foehring, “Kv2 subunits underlie slowly inactivating potassium current in rat neocortical pyramidal neurons,” Journal of Physiology, vol. 581, no. 3, pp. 941–960, 2007. View at Publisher · View at Google Scholar · View at Scopus
  201. D. Guan, L. R. Horton, W. E. Armstrong, and R. C. Foehring, “Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons,” Journal of Neurophysiology, vol. 105, no. 6, pp. 2976–2988, 2011. View at Publisher · View at Google Scholar
  202. M. Sitges, L. D. Possani, and A. Bayon, “Noxiustoxin, a short-chain toxin from the Mexican scorpion Centruroides noxius, induces transmitter release by blocking K+ permeability,” Journal of Neuroscience, vol. 6, no. 6, pp. 1570–1574, 1986. View at Google Scholar · View at Scopus
  203. G. D'Suze, C. V. F. Batista, A. Frau et al., “Discrepin, a new peptide of the sub-family α-KTx15, isolated from the scorpion Tityus discrepans irreversibly blocks K+-channels (IA currents) of cerebellum granular cells,” Archives of Biochemistry and Biophysics, vol. 430, no. 2, pp. 256–263, 2004. View at Publisher · View at Google Scholar · View at Scopus
  204. H. Vacher, R. Romi-Lebrun, C. Mourre et al., “A new class of scorpion toxin binding sites related to an A-type K+ channel: pharmacological characterization and localization in rat brain,” FEBS Letters, vol. 501, no. 1–3, pp. 31–36, 2001. View at Google Scholar · View at Scopus
  205. M. H. Li, Y. F. Wang, X. Q. Chen, N. X. Zhang, H. M. Wu, and G. Y. Hu, “BmTx3B, a novel scorpion toxin from Buthus martensi Karsch, inhibits delayed rectifier potassium current in rat hippocampal neurons,” Acta Pharmacologica Sinica, vol. 24, no. 10, pp. 1016–1062, 2003. View at Google Scholar · View at Scopus
  206. K. J. Swartz and R. MacKinnon, “An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula,” Neuron, vol. 15, no. 4, pp. 941–949, 1995. View at Publisher · View at Google Scholar · View at Scopus
  207. S. Diochot, M. D. Drici, D. Moinier, M. Fink, and M. Lazdunski, “Effects of phrixotoxins on the Kv4 family of potassium channels and implications for the role of Itoj in cardiac electrogenesis,” British Journal of Pharmacology, vol. 126, no. 1, pp. 251–263, 1999. View at Google Scholar · View at Scopus
  208. P. Escoubas, S. Diochot, M. L. Célérier, T. Nakajima, and M. Lazdunski, “Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies,” Molecular Pharmacology, vol. 62, no. 1, pp. 48–57, 2002. View at Publisher · View at Google Scholar · View at Scopus
  209. W. A. Schmalhofer, K. S. Ratliff, A. B. Weinglass, G. J. Kaczorowski, M. L. Garcia, and J. Herrington, “A KV2.1 gating modifier binding assay suitable for highthroughput screening,” Channels, vol. 3, no. 6, pp. 437–447, 2009. View at Google Scholar · View at Scopus
  210. J. Ebbinghaus, C. Legros, A. Nolting et al., “Modulation of Kv4.2 channels by a peptide isolated from the venom of the giant bird-eating tarantula Theraphosa leblondi,” Toxicon, vol. 43, no. 8, pp. 923–932, 2004. View at Publisher · View at Google Scholar · View at Scopus
  211. C. Kushmerick, E. Kalapothakis, P. S. L. Beirão et al., “Phoneutria nigriventer toxin Tx3-1 blocks A-type K+ currents controlling Ca2+ oscillation frequency in GH3 cells,” Journal of Neurochemistry, vol. 72, no. 4, pp. 1472–1481, 1999. View at Publisher · View at Google Scholar · View at Scopus
  212. C. W. Lee, S. Kim, S. H. Roh et al., “Solution structure and functional characterization of SGTx1, a modifier of Kv2.1 channel gating,” Biochemistry, vol. 43, no. 4, pp. 890–897, 2004. View at Google Scholar · View at Scopus
  213. O. B. McManus, “Calcium-activated potassium channels: regulation by calcium,” Journal of Bioenergetics and Biomembranes, vol. 23, no. 4, pp. 537–560, 1991. View at Google Scholar · View at Scopus
  214. C. Vergara, R. Latorre, N. V. Marrion, and J. P. Adelman, “Calcium-activated potassium channels,” Current Opinion in Neurobiology, vol. 8, no. 3, pp. 321–329, 1998. View at Publisher · View at Google Scholar · View at Scopus
  215. M. Schreiber and L. Salkoff, “A novel calcium-sensing domain in the BK channel,” Biophysical Journal, vol. 73, no. 3, pp. 1355–1363, 1997. View at Google Scholar · View at Scopus
  216. K. Yamamoto, K. Hashimoto, Y. Isomura, S. Shimohama, and N. Kato, “An IP3-assisted form of Ca2+-induced Ca2+ release in neocortical neurons,” NeuroReport, vol. 11, no. 3, pp. 535–539, 2000. View at Google Scholar · View at Scopus
  217. K. Yamamoto, K. Hashimoto, M. Nakano, S. Shimohama, and N. Kato, “A distinct form of calcium release down-regulates membrane excitability in neocortical pyramidal cells,” Neuroscience, vol. 109, no. 4, pp. 665–676, 2002. View at Publisher · View at Google Scholar · View at Scopus
  218. J. Shi, H. Q. He, R. Zhao et al., “Inhibition of martentoxin on neuronal BK channel subtype (α+β4): implications for a novel interaction model,” Biophysical Journal, vol. 94, no. 9, pp. 3706–3713, 2008. View at Publisher · View at Google Scholar · View at Scopus
  219. J. Garcia-Valdes, F. Z. Zamudio, L. Toro, and L. D. Possan, “Slotoxin, αKTx1.11, a new scorpion peptide blocker of MaxiK channels that differentiates between α and α+β (β1 or β4) complexes,” FEBS Letters, vol. 505, no. 3, pp. 369–373, 2001. View at Publisher · View at Google Scholar
  220. L. Vaca, G. B. Gurrola, L. D. Possani, and D. L. Kunze, “Blockade of a KCa channel with synthetic peptides from noxiustoxin: a K+ channel blocker,” Journal of Membrane Biology, vol. 134, no. 2, pp. 123–129, 1993. View at Google Scholar · View at Scopus
  221. K. Nhrke, C. C. Quinn, and T. Begenisich, “Molecular identification of Ca2+-activated K+ channels in parotid acinar cells,” American Journal of Physiology, vol. 284, no. 2 53-2, pp. C535–C546, 2003. View at Google Scholar
  222. G. G. Chicchi, G. Gimenez-Callego, E. Ber, M. L. Garcia, R. Winquist, and M. A. Cascieri, “Purification and characterization of a unique, potent inhibitor of apamin binding from Leiurus quinquestriatus hebraeus venom,” Journal of Biological Chemistry, vol. 263, no. 21, pp. 10192–10197, 1988. View at Google Scholar · View at Scopus
  223. P. Pedarzani, D. D'Hoedt, K. B. Doorty et al., “Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and afterhyperpolarization currents in central neurons,” Journal of Biological Chemistry, vol. 277, no. 48, pp. 46101–46109, 2002. View at Publisher · View at Google Scholar · View at Scopus