Inhibition of 2-Aminoethoxydiphenyl Borate-induced Rat Atrial Ectopic Activity by Anti-arrhythmic Drugs

Cellular Physiology and Biochemistry

关键词: 2-aminoethoxydiphenyl borate;    Anti-arrhythmic drugs;    Ectopic activity;    Atria;   

DOI  :  10.1159/000303047

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims 2-aminoethoxydiphenyl borate (2-APB) provokes spontaneous mechanical activity in isolated rat left atria. The present study is to characterize 2-APB-induced ectopic activity in rat atria and to investigate the inhibition of 2-APB-induced ectopic activity by anti-arrhythmic drugs. Methods 2-APB-induced ectopic activity was measured through an isometric force transducer connected to a multichannel acquisition and analysis system. Intracellular [Ca²⁺]_i was measured with fluorescence laser scanning confocal microscopy. Voltage-dependent L- type Ca²⁺ currents were recorded by using patch-clamp technique. Results 2-APB dose-dependently increased the ectopic activity of left atria at 1, 5, 10, 20, 50 µM. Anti-arrhythmic drugs, quinidine (10µM), lidocaine (10µM), verapamil (5µM), and amiodarone (50µM,100µM) inhibited 2-APB-induced ectopic activity. 2-APB-induced ectopic activity was inhibited by Ca²⁺-free bath, Na⁺/Ca²⁺ exchanger blockers, 3′,4′-dichlorobenzamil hydrochloride (DHC) and Ni²⁺, not by non-selective cation channel blocker Gd³⁺. 2-APB also induced ectopic contractions in ventricular tissue straps and the ectopic contractions were inhibited by quinidine, verapamil and DHC. Lidocaine, verapamil and DHC inhibited 2-APB-induced increase of intracellular Ca²⁺ concentration in cardiomyocytes. Low molecular weight heparin inhibited phenylephrine (PE)-induced but not 2-APB -induced atria ectopic activity, and the pattern of 2-APB-induced ectopic activity was continuous, distinct from the discontinuous activity induced by PE. Conclusion 2-APB-induced atria ectopic activity was inhibited by classic anti-arrhythmic drugs quinidine, lidocaine, verapamil, amiodarone, and Na⁺/Ca²⁺ exchanger blockers. It can be used for testing agents able to affect any of Na⁺, Ca²⁺ channel, Na⁺/Ca²⁺ exchanger without selectivity.

【 授权许可】

CC BY-NC-ND