Involvement of the Na+/Ca2+ exchanger in ouabain-induced inotropy and arrhythmogenesis in guinea-pig myocardium as revealed by SEA0400.
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.
Tanaka
Hikaru
H
Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Funabashi, Chiba 274-8510, Japan. htanaka@phar.toho-u.ac.jp
Shimada
Hideaki
H
Namekata
Iyuki
I
Kawanishi
Toru
T
Iida-Tanaka
Naoko
N
Shigenobu
Koki
K
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002460:Cell Line; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology*; D010210:Papillary Muscles; D010647:Phenyl Ethers / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000502:physiology*
D000814:Aniline Compounds; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D010647:Phenyl Ethers; D010726:Phosphodiesterase Inhibitors; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D010042:Ouabain; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine