Involvement of the Na+/Ca2+ Exchanger in Ouabain-Induced Inotropy and Arrhythmogenesis in Guinea-Pig Myocardium as Revealed by SEA0400

Journal of Pharmacological Sciences

Hikaru Tanaka¹  Iyuki Namekata¹  Toru Kawanishi²  Hideaki Shimada¹  Naoko Iida-Tanaka¹  Koki Shigenobu¹ 

[1] Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan;Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Japan

关键词: ouabain;    Na+/Ca2+ exchanger;    SEA0400;    inotropy;    arrhythmia;   

DOI  :  10.1254/jphs.FP0060911

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(26)Cited-By(14)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 μM SEA0400, which specifically inhibits the Na+/Ca2+ exchanger by 80%, reduced the ouabain (1 μM)-induced positive inotropy by 40%, but had no effect on the inotropy induced by 100 μM isobutyl methylxantine. SEA0400 significantly inhibited the contracture induced by low Na+ solution. In HEK293 cells expressing the Na+/Ca2+ exchanger, 1 μM ouabain induced an increase in intracellular Ca2+, which was inhibited by SEA0400. The arrhythmic contractions induced by 3 μM ouabain were significantly reduced by SEA0400. These results provide pharmacological evidence that the Na+/Ca2+ exchanger is involved in ouabain-induced inotropy and arrhythmogenesis.

【 授权许可】

Unknown