Hydrogen Sulfide Signaling in Oxidative Stress and Aging DevelopmentView this Special Issue
Review Article | Open Access
Weihua Zhang, Changqing Xu, Guangdong Yang, Lingyun Wu, Rui Wang, "Interaction of H2S with Calcium Permeable Channels and Transporters", Oxidative Medicine and Cellular Longevity, vol. 2015, Article ID 323269, 7 pages, 2015. https://doi.org/10.1155/2015/323269
Interaction of H2S with Calcium Permeable Channels and Transporters
A growing amount of evidence has suggested that hydrogen sulfide (H2S), as a gasotransmitter, is involved in intensive physiological and pathological processes. More and more research groups have found that H2S mediates diverse cellular biological functions related to regulating intracellular calcium concentration. These groups have demonstrated the reciprocal interaction between H2S and calcium ion channels and transporters, such as L-type calcium channels (LTCC), T-type calcium channels (TTCC), sodium/calcium exchangers (NCX), transient receptor potential (TRP) channels, β-adrenergic receptors, and N-methyl-D-aspartate receptors (NMDAR) in different cells. However, the understanding of the molecular targets and mechanisms is incomplete. Recently, some research groups demonstrated that H2S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions. In this review, we elucidate that H2S controls intracellular calcium homeostasis and the underlying mechanisms.
Hydrogen sulfide (H2S) was thought for hundreds of years to be a toxic gas that smelled like rotten eggs, but the gas is now believed to be a molecule involved in intensive physiological and pathological processes , such as protecting the heart against acute myocardial infarction [2, 3] and ischemia/hypoxia injury, regulating blood pressure , mediating smooth-muscle relaxation , and inhibiting insulin release and renin activity [6, 7]. H2S, as an endogenous gasotransmitter, can be mainly generated by pyridoxal-5′-phosphate- (PLP-) dependent cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), which interconvents the sulfuration from intracellular L-methionine and L-cysteine to produce H2S . In addition, 3-mercaptopyruvate sulfurtransferase (3-MST) and cysteine aminotransferase (CAT) produce H2S from cysteine through the combined actions of both enzymes .
An increasing amount of evidence has demonstrated that H2S regulates cellular biological signaling through modulating calcium ion channels and their related transporters [10, 11], such as L-type calcium channels (LTCC), T-type calcium channels (TTCC), sodium/calcium exchangers (NCX), transient receptor potential (TRP), β-adrenergic receptors, and NMDA receptors. This review presents the current research on H2S to better understand its regulation of calcium channels, with a special emphasis on mechanisms.
2. The Regulatory Mechanism of Interacting with Calcium ion Channels
2.1. Voltage-Dependent Calcium Channels (VDCC)
Ca2+ serves as an important second messenger in both excitable and nonexcitable cells. Voltage-dependent calcium channels (VDCC), store-operated calcium channels (SOCs), and G-protein coupled receptors (GPCRs) are responsible for calcium influx from extracellular fluids. Alterations in intracellular calcium levels trigger physiological responses, including cardiac muscle contraction, vascular dilatation, hormone secretion, and neurotransmitter release [12–16].
The family of VDCCs includes L-, T-, N-, and P/Q-subtypes, which differ in their cellular and subcellular distributions and functional properties [17, 18]. For example, T-type calcium channels (TTCCs) are involved in regulating cellular excitability , N and P/Q type channels mediate fast evoked neurotransmitter release , and L-type calcium channels (LTCCs) mediate excitation-contraction coupling in the heart and muscles, insulin secretion, and calcium-dependent gene transcription .
LTCCs are integral in excitation/contraction coupling and are one of the main channels for extracellular Ca2+ influx in myocardial cells. In 2002, Zhao and Wang first reported that H2S could directly inhibit calcium influx from LTCCs in smooth-muscle cells . Moreover, in 2009, Sun et al. further demonstrated that H2S, as a novel inhibitor of LTCC, has negative inotropic effects in rat cardiomyocytes . In a recent study, Avanzato et al. investigated the role of H2S in regulating VDCCs and the related functional effects on the cardiomyoblast cell line H9c2. They found that H2S inhibits LTCCs and TTCCs in H9c2. Pretreatment with NaHS (a donor of H2S) prevented cell death via H2O2 through inhibiting LTCCs. Their results were the first to demonstrate that H2S protects rat cardiomyoblasts against oxidative stress through inhibition of LTCCs . In addition, Tang et al. suggested that exogenous and endogenous H2S inhibited pancreatic insulin secretion by inhibiting LTCCs activity. They confirmed that NaHS reversibly decreased LTCC current density in a concentration-dependent manner in CSE WT pancreatic beta cells. Furthermore, they observed that DL-propargylglycine (an inhibitor of CSE) increased the basal LTCC activity in beta cells from CSE WT mice, but not in pancreatic beta cells from CSE-KO mice. Pancreatic beta cells from CSE-KO mice displayed a higher LTCCs density than those from WT mice. These results suggested that a novel mechanism for regulating insulin secretion was related to the CSE/H2S system, which controlled LTCC activity . Recently, some data showed that exogenous and endogenous H2S can modify cystein residues of different proteins through S-sulfhydration. The –SH from sulfhydryl donor is transformed to free cysteine sulfhydryl and forms covalent persulfide (–SSH) [25, 26]. In 2012, Zhang and his coworkers showed that NaHS inhibited the peak amplitude of the L-type calcium current in a concentration-dependent manner and could be partly inhibited by the oxidant sulfhydryl modifier diamide (DM). They explained that dithiothreitol (DTT), a reductant that transforms disulfide bridges into sulfhydryl groups in cysteine-containing proteins, could significantly reverse NaHS-induced inhibition of calcium current from LTCCs. Their results suggested that H2S inhibited L-type calcium currents depending on the sulfhydryl group in rat cardiomyocytes  (Figure 1).
TTCCs are classified into three T-type channel subtypes, Cav3.1, Cav3.2, and Cav3.3. There have been reports about the T-type channels being activated by H2S in neurons [28–30]. In the pain pathways, Cav3.2 in the peripheral terminals of nociceptors and dorsal horn spinal neurons appears to promote peripheral nociception and central nociceptive sensitization . H2S may function as a neuromodulator in sensory transmission. There is evidence that chemotherapy-induced neuropathic pain is blocked by ethosuximide, which is known to block TTCCs. Systemic administration of DL-propargylglycine and β-cyanoalanine, irreversible and reversible inhibitors of CSE, respectively, also abolished neuropathic pain. Okubo et al. demonstrated that 3.2 and CSE at the protein level are upregulated, which induced a significant increase in H2S level. H2S facilitated pain sensation by targeting 3.2 TTCCs. The H2S/3.2 pathway appears to play a role in the maintenance of surgically evoked neuropathic pain . Intraplantar administration of NaHS causes mechanical hyperalgesia in rats, an effect reversed by mibefradil (a T-type Ca2+ channel blocker), and also enhances membrane currents through the TTCC in NG 108-15 cells and mouse dorsal root ganglion neurons [29, 30]. Their data suggested that spinal and peripheral NaHS/H2S facilitates the expression of Cav3.2 TTCCs in the primary afferent and/or spinal nociceptive neurons, leading to sensitization of nociceptive processing and hyperalgesia . Sekiguchi et al. demonstrated that endogenous and exogenous hydrogen sulfide facilitate T-type calcium channel currents in Cav3.2-expressing HEK293 cells . In contrast, Elies et al. reported an inhibitory effect with high doses of NaHS on Cav3.2-overexpressing HEK cells . Their data were the first preliminary evidence that H2S negatively modulates endogenously expressed TTCCs in a myoblast cell line. In spite of the opposite opinion in the effects of NaHS on TTCCs in different research groups, H2S regulating the activity of TTCC has been confirmed widely. However, most of the evidence suggests that H2S elevates the activities of TTCCs and increases the amplitudes of T-type Ca2+ currents in different cell lines.
2.2. β-Adrenergic Receptors
Cardiac excitation-contraction coupling is under the direct control of the adrenergic nervous system. In the heart, the β-adrenergic receptor (AR), a G-protein coupled receptor, activates the associated adenylyl cyclase (AC)-cAMP-protein kinase A (PKA) pathway . β-Adrenoceptor-coupled stimulatory G proteins lead to an increased intracellular cAMP level and stimulate protein kinase A (PKA) to mediate phosphorylation of LTCCs and finally increase contractile function [35–37]. Some reports have observed that H2S content in the heart was significantly reduced in a cardiac ischemia  and overstimulation of the β-adrenergic system by isoproterenol (ISO, β-adrenoceptor agonist) models . Yong and his coworkers revealed that H2S may negatively modulate β-adrenoceptor function via inhibiting adenylyl cyclase activity . They found that ISO (10−9–10−6 M), in a concentration-dependent manner, increased the twitch amplitude of ventricular myocytes, which was attenuated by NaHS (10−5–10−3 M) in a dose-dependent manner. The amplitudes and maximal velocities (±dL/dt) for myocyte twitch and transient amplitudes were enhanced by ISO, forskolin (an adenylyl cyclase activator), 8-bromoadenosine-3′,5′-cyclic monophosphate (an activator of protein kinase A), and Bay K-8644 (a selective LTCC agonist). Administration of NaHS (100 μM) significantly attenuated the effects of only ISO and forskolin. Moreover, NaHS reversed the ISO-induced cAMP increase and forskolin-stimulated adenylyl cyclase activity. Thus, they postulated that H2S may negatively regulate β-AR function through inhibition of the cAMP/PKA pathway. In addition, some studies found that the plasma concentration of H2S in patients with coronary heart disease  and in the setting of ISO overstimulation significantly decreased endogenous H2S production, which implies that a reduced H2S level caused by ischemia and β-adrenoceptor overstimulation may result in impairment of the negative modulation of H2S on the β-adrenoceptor system and hence calcium overload.
2.3. Sodium Calcium Exchanger (NCX)
The sodium calcium exchanger (NCX) is one of the key players in the regulation of intracellular calcium homeostasis. In a physiological condition, NCX, a nonselective cation channel, may induce the influx of 3 Na+ into cells in exchange for the efflux of 1 Ca2+ . However, in pathological conditions, such as ischemia/reperfusion, hypoxia, and heart failure, NCX function could be reversed, with one Ca2+ moving inward and three molecules of Na+ going out of the cell . H2S may stimulate Ca2+ influx into endothelial cells (ECs) by recruiting the reverse-mode for the NCX [44–46]. To confirm the role of NCX in NaHS-dependent Ca2+ signaling, KB-R 7943 (20 μM), a selective inhibitor of the reverse-mode, was used in the experiment. Moccia and his coworkers’ data showed that NaHS failed to elicit a elevation in ECs pretreated with KB-R 7943. In addition, the amplitude of the Ca2+ response was significantly lower in ECs activated by the H2S donor in the presence of KB-R 7943. Taken together, these findings hinted at NCX as a key mediator of NaHS-elicited Ca2+ inflow in rat aortic ECs. To further determine the effect of sulfide signaling on the NCX, several studies investigated NCX expression and function in HeLa cells. They observed increased levels of NCX1 mRNA, protein, and activity after 24 h of GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino) phosphinodithioate, a slow releasing H2S donor) treatment. This increase was accompanied by elevated cAMP due to GYY4137 treatment, which was completely abolished when NCX1 was silenced. An increased cAMP level would point to upregulation of the β-adrenergic receptors. Thus, Cheng et al. investigated the relationship of β-adrenergic receptors with the NCX1 in the presence and/or absence of H2S and determined the physiological importance of this potential communication using GYY4137 . Indeed, GYY4137 increased expression of the β1 and β3 (but not β2) adrenergic receptors, suggesting that sulfide signaling played a role in regulating the NCX1 and β1 and β3 adrenergic receptors and their colocalization.
2.4. Transient Receptor Potential (TRP) Channels
A growing body evidence has shown that H2S and neuronal excitation induce calcium ion influx in astrocytes, and the interaction between neurons and astrocytes regulates synaptic activity [48–50]. TRP channels were found to mediate the responses to H2S in the urinary bladder and sensory neurons . Although the effects of H2S on transient receptor potential (TRP) channels are not completely clear, Kimura et al. demonstrated that polysulfides of H2S-derived signaling molecules stimulated TRP channels in the brain . They suggested that H2S induced Ca2+ influx in astrocytes through generating polysulfides of TRP. They administered sodium polysulfides, Na2S3, in their experiments, which induced Ca2+ influx in a concentration-dependent manner. They also confirmed that this astrocyte response to H2S was suppressed by the TRP channel blockers La3+ and Gd3+. To further reveal the mechanism for Na2S3-induced TRP channel opening, the TRPA1 channel inhibitors HC-030031 and AP-18 and TRPA1 siRNA were used. Their data showed that, in the presence of the inhibitors or TRPA1 siRNA, Na2S3 could not induce Ca2+ influx through the TRPA1 channel. Liu et al. showed that H2S maintained mesenchymal stem cell function via regulation of Ca2+ channel sulfhydration . They found that NaHS-treated bone marrow mesenchymal stem cells (BMMSCs) induced Ca2+ influx with a limited contribution from intracellular Ca2+ storage. They also found that DTT, by reducing the disulfide bonds in proteins and increasing the number of residual sulfhydryl proteins, elevated NaHS-induced Ca2+ influx in BMMSCs. Diamide, by reducing the number of sulfhydryls and 2-sulfonatoe-methanethiosulfonate (MTSES), a nonpermeable reagent able to reduce free sulfhydryls only on the outer cytomembrane, could reduce NaHS-induced Ca2+ influx in BMMSCs. These results revealed that free sulfhydryls affect NaHS-induced Ca2+ influx. The above results suggested that polysulfides, as H2S-derived bioactive molecules, stimulate TRP channels, providing a new molecular mechanism for sulfide-induced signaling.
2.5. N-Methyl-D-aspartate Receptors (NMDARs)
N-Methyl-D-aspartate receptors (NMDARs) form glutamate-gated ion channels that are widely expressed in the central nervous system and are highly permeable to calcium ions, which are essential for regulating synaptogenesis, use-dependent synaptic remodeling, and long-term plastic changes in synaptic strength . H2S, as a neuromodulator, elevates the activity of N-methyl-D-aspartate (NMDA) receptors to facilitate the induction of hippocampal long-term potentiation (LTP), a synaptic model of memory formation [48, 55]. Nagai et al. demonstrated that H2S enhances the neuronal response to glutamate and induces Ca2+ waves in astrocytes . Glial cells communicate with surrounding cells by increasing the intracellular concentration of Ca2+ and propagating the signal as Ca2+ waves that occur in glia, and neurons show Ca2+ oscillations and intracellular Ca2+ waves. Because astrocytes elicit intracellular Ca2+ waves by electrical stimulation and application of NMDA in mixed cultures of neurons and astrocytes, astrocytes have been suggested to respond directly to a neurotransmitter released from neurons excited by NMDA or electrical stimulation [56–59]. La2+ and Gd3+ block Ca2+ waves and inhibit Ca2+ channels; La2+ and Gd3+ may inhibit the exocytosis of glutamate or some factor from neurons when neurons are stimulated by NMDA. However, La2+ and Gd3+ block H2S-initiated waves in pure astrocyte culture, showing that Ca2+ is most likely involved in the propagation step. H2S released in response to neuronal excitation may activate Ca2+ channels to induce Ca2+ waves in astrocytes. H2S may therefore mediate signals between neurons and glia. H2S is released from neurons or glia by neuronal excitation and increases the intracellular concentration of Ca2+ by activating Ca2+ channels in astrocytes and to a lesser extent causes release from intracellular Ca2+ stores. An elevated intracellular Ca2+ triggers the induction of Ca2+ waves that propagate to the neighboring astrocytes [60–63]. H2S enhances the activity of NMDA receptors by reducing the cysteine disulfide bond in the hinge region of the ligand-binding domain of NMDA receptors, and polysulfides further enhance this activity by adding bound sulfane sulfur to the receptors. Polysulfides activate the TRPA1 channels in astrocytes to induce Ca2+ influx, which facilitates the release of the gliotransmitter D-serine to enhance the activity of NMDA receptors. By these integrated mechanisms, H2S along with polysulfides may facilitate the induction of LTP .
3. Conclusions and Perspective
An increasing amount of evidence has clearly demonstrated that H2S is associated with relevant biological processes, such as cardiac systolic function, sensory transduction, antiapoptotic function, and neuroprotection . These functions are closely related to H2S regulating various calcium ion channels and transporters . Many studies cited in this review investigated the fact that polysulfides of calcium ion channels, which are modified by H2S, have been found to elevate the activity of TRP, TTCC, and NMDARs and to inhibit LTCC through the mechanism of sulfhydration. Furthermore, H2S could upregulate the activities of the NCX1 and β1 and β3 adrenergic receptors and their colocalization. Altered effects of H2S on calcium ion channels under different pathophysiological conditions are being investigated. Extensive research on the mechanisms of H2S modulation of calcium signaling will provide new insights into the physiological function of H2S.
Conflict of Interests
No conflict of interests, financial or otherwise, was declared by any of the authors.
This work was supported by the National Natural Science Foundation of China (nos. 81170289 and 81370421).
- G. K. Kolluru, X. Shen, and C. G. Kevil, “A tale of two gases: NO and H2S, foes or friends for life?” Redox Biology, vol. 1, no. 1, pp. 313–318, 2013.
- C. C. Shin, P. K. Moore, and Y. Z. Zhu, “S-allylcysteine mediates cardioprotection in an acute myocardial infarction rat model via a hydrogen sulfide-mediated pathway,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 293, no. 5, pp. H2693–H2701, 2007.
- Q. Wang, X.-L. Wang, H.-R. Liu, P. Rose, and Y.-Z. Zhu, “Protective effects of cysteine analogues on acute myocardial ischemia: novel modulators of endogenous H2S production,” Antioxidants & Redox Signaling, vol. 12, no. 10, pp. 1155–1165, 2010.
- G. D. Yang, L. Y. Wu, B. Jiang et al., “H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine γ-lyase,” Science, vol. 322, no. 5901, pp. 587–590, 2008.
- G. Tang, L. Wu, and R. Wang, “Interaction of hydrogen sulfide with ion channels,” Clinical and Experimental Pharmacology and Physiology, vol. 37, no. 7, pp. 753–763, 2010.
- L. Wu, W. Yang, X. Jia et al., “Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats,” Laboratory Investigation, vol. 89, no. 1, pp. 59–67, 2009.
- M. Lu, Y.-H. Liu, H. S. Goh et al., “Hydrogen sulfide inhibits plasma renin activity,” Journal of the American Society of Nephrology, vol. 21, no. 6, pp. 993–1002, 2010.
- Q.-H. Gong, X.-R. Shi, Z.-Y. Hong, L.-L. Pan, X.-H. Liu, and Y.-Z. Zhu, “A new hope for neurodegeneration: possible role of hydrogen sulfide,” Journal of Alzheimer's Disease, vol. 24, supplement 2, no. 1, pp. 173–182, 2011.
- N. Shibuya, M. Tanaka, M. Yoshida et al., “3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain,” Antioxidants & Redox Signaling, vol. 11, no. 4, pp. 703–714, 2009.
- J. Markova, S. Hudecova, A. Soltysova et al., “Sodium/calcium exchanger is upregulated by sulifide signaling, forms complex with the β1 and β3 but not β2 adrenergrc receptors, and induces apoptosis,” Pflugers Archiv: European Journal of Physiology, vol. 466, no. 1, pp. 1329–1342, 2014.
- N. R. Prabhakar, “Hydrogen sulfide (H2S): a physiologic mediator of carotid body response to hypoxia,” Advances in Experimental Medicine and Biology, vol. 758, pp. 109–113, 2012.
- D. B. Wheeler, A. Randall, and R. W. Tsien, “Roles of N-type and Q-type Ca2+ channels in supporting hippocampal synaptic transmission,” Science, vol. 264, no. 5155, pp. 107–111, 1994.
- R. E. Dolmetsch, U. Pajvani, K. Fife, J. M. Spotts, and M. E. Greenberg, “Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway,” Science, vol. 294, no. 5541, pp. 333–339, 2001.
- L. Cribbs, “T-type calcium channel expression and function in the diseased heart,” Channels, vol. 4, no. 6, pp. 447–452, 2010.
- C. Seisenberger, V. Specht, A. Welling et al., “Functional embryonic cardiomyocytes after disruption of the L-type α1C (Cav1.2) calcium channel gene in the mouse,” Journal of Biological Chemistry, vol. 275, no. 50, pp. 39193–39199, 2000.
- R. W. Turner, D. Anderson, and G. W. Zamponi, “Signaling complexes of voltage-gated calcium channels,” Channels, vol. 5, no. 5, pp. 440–448, 2011.
- W. A. Catterall, “Structure and regulation of voltage-gated Ca2+ channels,” Annual Review of Cell and Developmental Biology, vol. 16, pp. 521–555, 2000.
- D. Kim, I. Song, S. Keum et al., “Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking α1G T-type Ca2+ channels,” Neuron, vol. 31, no. 1, pp. 35–45, 2001.
- S. M. Cain and T. P. Snutch, “Contributions of T-type calcium channel isoforms to neuronal firing,” Channels, vol. 4, no. 6, pp. 475–482, 2010.
- T. Tanabe, A. Mikami, S. Numa, and K. G. Beam, “Cardiac-type excitation-contraction coupling in dysgenic skeletal muscle injected with cardiac dihydropyridine receptor cDNA,” Nature, vol. 344, no. 6265, pp. 451–453, 1990.
- W. Zhao and R. Wang, “H2S-induced vasorelaxation and underlying cellular and molecular mechanisms,” The American Journal of Physiology—Heart and Circulatory Physiology, vol. 283, no. 2, pp. H474–H480, 2002.
- Y.-G. Sun, Y.-X. Cao, W.-W. Wang, S.-F. Ma, T. Yao, and Y.-C. Zhu, “Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes,” Cardiovascular Research, vol. 79, no. 4, pp. 632–641, 2008.
- D. Avanzato, A. Merlino, S. Porrera, R. Wang, L. Munaron, and D. Mancardi, “Role of calcium channels in the protective effect of hydrogen sulfide in rat cardiomyoblasts,” Cellular Physiology and Biochemistry, vol. 33, no. 4, pp. 1205–1214, 2014.
- G. Tang, L. Zhang, G. Yang, L. Wu, and R. Wang, “Hydrogen sulfide-induced inhibition of L-type Ca2+ channels and insulin secretion in mouse pancreatic beta cells,” Diabetologia, vol. 56, no. 3, pp. 533–541, 2013.
- L. Li, P. Rose, and P. K. Moore, “Hydrogen sulfide and cell signaling,” Annual Review of Pharmacology and Toxicology, vol. 51, pp. 169–187, 2011.
- A. K. Mustafa, M. M. Gadalla, N. Sen et al., “H2S signals through protein S-Sulfhydration,” Science Signaling, vol. 2, no. 96, article ra72, 2009.
- R. Y. Zhang, Y. Sun, H. J. Tsai, C. S. Tang, H. F. Jin, and J. B. Du, “Hydrogen sulfide inhibits L-type calcium currents depending upon the protein sulfhydryl state in rat cardiomyocytes,” PLoS ONE, vol. 7, no. 5, Article ID e37073, 2012.
- K. Okubo, M. Matsumura, Y. Kawaishi et al., “Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice,” British Journal of Pharmacology, vol. 166, no. 5, pp. 1738–1743, 2012.
- A. Kawabata, “Novel functions of hydrogen sulphide through T-type calcium channels: its involvement in pain processing,” Journal of pharmacol ogical Sciences, vol. 106, no. 4, pp. 479–488, 2008.
- Y. Maeda, Y. Aoki, F. Sekiguchi et al., “Hyperalgesia induced by spinal and peripheral hydrogen sulfide: evidence for involvement of Cav3.2 T-type calcium channels,” Pain, vol. 142, no. 1-2, pp. 127–132, 2009.
- K. Okubo, T. Takahashi, F. Sekiguchi et al., “Inhibition of T-type calcium channels and hydrogen sulfide-forming enzyme reverses paclitaxel-evoked neuropathic hyperalgesia in rats,” Neuroscience, vol. 188, pp. 148–156, 2011.
- F. Sekiguchi, Y. Miyamoto, D. Kanaoka et al., “Endogenous and exogenous hydrogen sulfide facilitates T-type calcium channel currents in Cav3.2-expressing HEK293 cells,” Biochemical Biophysical Research Communication, vol. 445, no. 1, pp. 225–228, 2014.
- J. Elies, J. L. Scragg, D. Huang, M. Dallas, J. P. Boyle, and C. Peers, “Hydrogen sulfide inhibits Cav3.2 T-type Ca2+ channels,” The FASEB Journal, 2014.
- D. Ho, L. Yan, K. Iwatsubo, D. E. Vatner, and S. F. Vatner, “Modulation of β-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5,” Heart Failure Reviews, vol. 15, no. 5, pp. 495–512, 2010.
- D. M. Bers, “Cardiac excitation-contraction coupling,” Nature, vol. 415, no. 6868, pp. 198–205, 2002.
- D. M. Bers, “Calcium cycling and signaling in cardiac myocytes,” Annual Review of Physiology, vol. 70, pp. 23–49, 2008.
- S. T. Rapundalo, “Cardiac protein phosphorylation: functional and pathophysiological correlates,” Cardiovascular Research, vol. 38, no. 3, pp. 559–588, 1998.
- J.-S. Bian, C. Y. Qian, T.-T. Pan et al., “Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes,” Journal of Pharmacology and Experimental Therapeutics, vol. 316, no. 2, pp. 670–678, 2006.
- B. Geng, L. Chang, C. Pan et al., “Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol,” Biochemical and Biophysical Research Communications, vol. 318, no. 3, pp. 756–763, 2004.
- Q. C. Yong, T.-T. Pan, L.-F. Hu, and J.-S. Bian, “Negative regulation of β-adrenergic function by hydrogen sulphide in the rat hearts,” Journal of Molecular and Cellular Cardiology, vol. 44, no. 4, pp. 701–710, 2008.
- H.-L. Jiang, H.-C. Wu, Z.-L. Li, B. Geng, and C.-S. Tang, “Changes of the new gaseous transmitter H2S in patients with coronary heart disease,” Di Yi Jun Yi Da Xue Xue Bao, vol. 25, no. 8, pp. 951–954, 2005.
- M. Ottolia, N. Torres, J. H. B. Bridge, K. D. Philipson, and J. I. Goldhaber, “Na/Ca exchange and contraction of the heart,” Journal of Molecular and Cellular Cardiology, vol. 61, no. 8, pp. 28–33, 2013.
- J. Weisser-Thomas, V. Piacentino, J. P. Gaughan, K. Margulies, and S. R. Houser, “Calcium entry via Na+/Ca2+ exchange during the action potential directly contributes to contraction of failing human ventricular myocytes,” Cardiovascular Research, vol. 57, no. 4, pp. 974–985, 2003.
- F. Moccia, G. Bertoni, A. F. Pla et al., “Hydrogen sulfide regulates intracellular Ca2+ concentration in endothelial cells from excised rat aorta,” Current Pharmaceutical Biotechnology, vol. 12, no. 9, pp. 1416–1426, 2011.
- M. Y. Ali, C. Y. Ping, Y. Y. P. Mok et al., “Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide?” British Journal of Pharmacology, vol. 149, no. 6, pp. 625–634, 2006.
- Y. Cheng, J. F. Ndisang, G. Tang, K. Cao, and R. Wang, “Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats,” American Journal of Physiology: Heart and Circulatory Physiology, vol. 287, no. 5, pp. H2316–H2323, 2004.
- K. Okubo, T. Takahashi, F. Sekiguchi et al., “Inhibition of T-type calcium channels and hydrogen sulfide-forming enzyme reverses paclitaxel-evoked neuropathic hyperalgesia in rats,” Neuroscience, vol. 188, pp. 148–156, 2011.
- K. Abe and H. Kimura, “The possible role of hydrogen sulfide as an endogenous neuromodulator,” The Journal of Neuroscience, vol. 16, no. 3, pp. 1066–1071, 1996.
- Y. Nagai, M. Tsugane, J.-I. Oka, and H. Kimura, “Hydrogen sulfide induces calcium waves in astrocytes,” The FASEB Journal, vol. 18, no. 3, pp. 557–559, 2004.
- H. Kimura, “Physiological role of hydrogen sulfide and polysulfide in the central nervous system,” Neurochemistry International, vol. 63, no. 5, pp. 492–497, 2013.
- H. Ogawa, K. Takahashi, S. Miura et al., “H2S functions as a nociceptive messenger through transient receptor potential ankyrin 1 (TRPA1) activation,” Neuroscience, vol. 218, pp. 335–343, 2012.
- Y. Kimura, Y. Mikami, K. Osumi, M. Tsugane, J.-I. Oka, and H. Kimura, “Polysulfides are possible H2S-derived signaling molecules in rat brain,” The FASEB Journal, vol. 27, no. 6, pp. 2451–2457, 2013.
- Y. Liu, R. Yang, X. Liu et al., “Hydrogen sulfide maintains mesenchymal stem cell function and bone homeostasis via regulation of Ca2+ channel sulfhydration,” Cell Stem Cell, vol. 15, no. 1, pp. 66–78, 2014.
- E. E. Benarroch, “NMDA receptors: recent insights and clinical correlations,” Neurology, vol. 76, no. 20, pp. 1750–1757, 2011.
- D. E. Baranano, C. D. Ferris, and S. H. Snyder, “Atypical neural messengers,” Trends in Neurosciences, vol. 24, no. 2, pp. 99–106, 2001.
- M. Nedergaard, “Direct signaling from astrocytes to neurons in cultures of mammalian brain cells,” Science, vol. 263, no. 5154, pp. 1768–1771, 1994.
- V. Parpura, T. A. Basarsky, F. Liu, K. Jeftinija, S. Jeftinija, and P. G. Haydon, “Glutamate-mediated astrocyte-neuron signalling,” Nature, vol. 369, no. 6483, pp. 744–747, 1994.
- E. A. Newman and K. R. Zahs, “Modulation of neuronal activity by glial cells in the retina,” The Journal of Neuroscience, vol. 18, no. 11, pp. 4022–4028, 1998.
- H. R. Parri, T. M. Gould, and V. Crunelli, “Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation,” Nature Neuroscience, vol. 4, no. 8, pp. 803–812, 2001.
- A. H. Cornell-Bell, S. M. Finkbeiner, M. S. Cooper, and S. J. Smith, “Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling,” Science, vol. 247, no. 4941, pp. 470–473, 1990.
- A. C. Charles, J. E. Merrill, E. R. Dirksen, and M. J. Sanderson, “Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate,” Neuron, vol. 6, no. 6, pp. 983–992, 1991.
- S. Duffy and B. A. MacVicar, “Adrenergic calcium signaling in astrocyte networks within the hippocampal slice,” The Journal of Neuroscience, vol. 15, no. 8, pp. 5535–5550, 1995.
- J. Kang, L. Jiang, S. A. Goldman, and M. Nedergaard, “Astrocyte-mediated potentiation of inhibitory synaptic transmission,” Nature Neuroscience, vol. 1, no. 8, pp. 683–692, 1998.
- H. Kimura, “The physiological role of hydrogen sulfide and beyond,” Nitric Oxide, vol. 41, pp. 4–10, 2014.
- R. Wang, “Physiological implications of hydrogen sulfide: a whiff exploration that blossomed,” Physiological Reviews, vol. 92, no. 2, pp. 791–896, 2012.
- L. Munaron, D. Avanzato, F. Moccia, and D. Mancardi, “Hydrogen sulfide as a regulator of calcium channels,” Cell Calcium, vol. 53, no. 2, pp. 77–84, 2013.
Copyright © 2015 Weihua Zhang 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.