Arrhythmogenic effects of isoproterenol-activated Cl- current in guinea-pig ventricular myocytes

Possible arrhythmogenic effects of the isoproterenol-activated Cl- current were examined in isolated guinea-pig ventricular myocytes under various intra- and extracellular Cl- concentrations. Experiments were carried out with external K+ concentration ([K+]o) decreased to 2 or 3 mM. Under symmetrical concentrations of Cl- in intra- and extra-cellular solutions (ECl = 0 mV), 1 microM isoproterenol (ISP) depolarized resting membrane potential (RMP) by 6.2 +/- 1.1 mV and slowed repolarization with induction of early afterdepolarizations (EADs) in 9 out of 9 cells. EADs appeared at voltages positive to -40 mV, where L-type Ca2+ current is assumed to be activated. When Cl- concentrations were settled near physiological conditions (ECl = -40 - -50 mV), ISP depolarized RMP by 2.8 +/- 0.4 mV and elicited abnormal repolarization with occasional EADs in 6 out of 19 cells. When ECl was set to -80 mV, however, ISP depolarized RMP by only 0.5 +/- 0.5 mV without induction of abnormal activities. Thus, depolarizing effects of ISP and incidence of repolarization abnormalities including EADs were increased as ECl shifted to more positive potential levels. At [K+]o = 4 mM, no abnormal activities were observed when ECl was around -50 mV (0/8), and 6 out of 6 cells showed abnormal activities when ECl was set to 0 mV. ISP-elicited abnormal activities were abolished by 1 mM DNDS (4,4'-dinitrostilbene-2,2'-disulphonic acid), a blocker for Cl- channels.(ABSTRACT TRUNCATED AT 250 WORDS)