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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 803082, 9 pages
http://dx.doi.org/10.1155/2012/803082
Research Article

The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker

1Tian-Sheng Memorial Hospital, Tong-Kang, Pintong, Taiwan
2School of Biomedical Sciences, Chung Shan Medical University, Taichung 402, Taiwan
3Department and Graduate Institute of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan
4Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

Received 2 December 2011; Accepted 12 January 2012

Academic Editor: Ke Ren

Copyright © 2012 Tzu-Rong Su 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.

Abstract

The purpose of this study was to investigate the effect of KCNQ (potassium channel, voltage-gated, KQT-like subfamily) openers in preventing myotonia caused by anthracene-9-carboxylic acid (9-AC, a chloride channel blocker). An animal model of myotonia can be elicited in murine skeletal muscle by 9-AC treatment. KCNQ openers, such as retigabine and flupirtine, can inhibit the increased twitch amplitude (0.1 Hz stimulation) and reduce the tetanic fade (20 Hz stimulations) observed in the presence of 9-AC. Furthermore, the prolonged twitch duration of skeletal muscle was also inhibited by retigabine or flupirtine. Lamotrigine (an anticonvulsant drug) has a lesser effect on the muscle twitch amplitude, tetanic fade, and prolonged twitch duration as compared with KCNQ openers. In experiments using intracellular recordings, retigabine and flupirtine clearly reduced the firing frequencies of repetitive action potentials induced by 9-AC. These data suggested that KCNQ openers prevent the myotonia induced by 9-AC, at least partly through enhancing potassium conductance in skeletal muscle. Taken together, these results indicate that KCNQ openers are potential alternative therapeutic agents for the treatment of myotonia.