SEA0400揭示了钠钙交换体在哇巴因诱导的豚鼠心肌变力作用和心律失常发生中的作用。
Involvement of the Na+/Ca2+ exchanger in ouabain-induced inotropy and arrhythmogenesis in guinea-pig myocardium as revealed by SEA0400.
作者信息
Tanaka Hikaru, Shimada Hideaki, Namekata Iyuki, Kawanishi Toru, Iida-Tanaka Naoko, Shigenobu Koki
机构信息
Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Funabashi, Chiba 274-8510, Japan.
出版信息
J Pharmacol Sci. 2007 Feb;103(2):241-6. doi: 10.1254/jphs.fp0060911.
Involvement of the Na+/Ca2+ exchanger in ouabain-induced inotropy and arrhythmogenesis was examined with a specific inhibitor, SEA0400. In right ventricular papillary muscle isolated from guinea-pig ventricle, 1 microM SEA0400, which specifically inhibits the Na+/Ca2+ exchanger by 80%, reduced the ouabain (1 microM)-induced positive inotropy by 40%, but had no effect on the inotropy induced by 100 microM isobutyl methylxantine. SEA0400 significantly inhibited the contracture induced by low Na+ solution. In HEK293 cells expressing the Na+/Ca2+ exchanger, 1 microM ouabain induced an increase in intracellular Ca2+, which was inhibited by SEA0400. The arrhythmic contractions induced by 3 microM ouabain were significantly reduced by SEA0400. These results provide pharmacological evidence that the Na+/Ca2+ exchanger is involved in ouabain-induced inotropy and arrhythmogenesis.
使用特异性抑制剂SEA0400研究了钠钙交换体在哇巴因诱导的心肌收缩力和心律失常发生中的作用。在从豚鼠心室分离的右心室乳头肌中，1微摩尔SEA0400可特异性抑制钠钙交换体80%，使哇巴因（1微摩尔）诱导的正性肌力作用降低40%，但对100微摩尔异丁基甲基黄嘌呤诱导的肌力作用无影响。SEA0400显著抑制低钠溶液诱导的挛缩。在表达钠钙交换体的HEK293细胞中，1微摩尔哇巴因诱导细胞内钙离子增加，SEA0400可抑制这一增加。SEA0400显著减少了3微摩尔哇巴因诱导的心律失常性收缩。这些结果提供了药理学证据，表明钠钙交换体参与了哇巴因诱导的心肌收缩力和心律失常发生。
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