The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker
The Effects of the KCNQ Openers Retigabine and Flupirtine on Myotonia in Mammalian Skeletal Muscle Induced by a Chloride Channel Blocker
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DOI：
10.1155/2012/803082
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Lin, Min-Jon
中科院分区：
文献类型：
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作者：
Su, Tzu-Rong;Zei, Wen-Shan;Lin, Min-Jon
本研究旨在探讨KCNQ（钾通道，电压门控，KQT样亚家族）开放剂对蒽-9-羧酸（9-AC，氯通道阻断剂）所致肌强直的预防作用。通过9-AC处理可以在鼠骨骼肌中引发肌强直的动物模型。KCNQ开放剂，如瑞替加滨和氟吡汀，可以抑制增加的抽搐幅度（0.1 Hz刺激），并减少强直消退（20 Hz刺激）观察到的9-AC的存在。此外，延长骨骼肌的抽搐时间也被retigabine或flupirtine抑制。拉莫三嗪（一种抗惊厥药物）与KCNQ开放剂相比，对肌肉抽搐幅度、强直消退和抽搐持续时间的影响较小。在使用细胞内记录的实验中，瑞替加滨和氟吡汀明显降低了9-AC诱导的重复动作电位的放电频率。这些数据表明，KCNQ开放剂防止由9-AC诱导的肌强直，至少部分地通过增强骨骼肌中的钾电导。总之，这些结果表明，KCNQ开放剂是治疗肌强直的潜在替代治疗剂。
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.