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

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 microM. Anti-arrhythmic drugs, quinidine (10 microM), lidocaine (10 microM), verapamil (5 microM), and amiodarone (50 microM, 100 microuM) 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.