AUTOMATIC ACTIVITY IN DEPOLARIZED GUINEA-PIG VENTRICULAR MYOCARDIUM - CHARACTERISTICS AND MECHANISMS

Membrane potential was changed uniformly in 0.7-1.0 mm segments of guinea pig papillary muscles excised from the right ventricle by using extracellular polarizing current pulses applied across 2 electrically insulated compartments. Rhythmic automatic depolarizations (RAD) occurred in 90% of preparations superfused with Tyrode''s solution at maximum diastolic membrane potentials ranging from -35.2 .+-. 7.5 (threshold) to +4.0 .+-. 9.2 mV. The average maximum dV/dt of RAD ranged from 17.1-18.0 V/s within a membrane potential range of -40 to +20 mV. Raising extracellular Ca2+ concentration [Ca2+]0 from 1.8 to 6.8 mM, or application of isoproterenol (10-6 g/ml) enhanced the rate of RAD, but lowering [Ca2+]0 to 0.4 mM or exposure to MnCl2 (6 mM) abolished RAD. RAD were enhanced by lowering extracellular K+ concentration [K+]0 from 5.4 to 1.5 mM. RAD were suppressed in 40% of fibers by raising [K+]0 to 15.4 mM and in all fibers by raising [K+]0 to 40.4 mM. This suppression was due to increased [K+]0 and not to K-induced depolarization because it persisted when membrane potential was held by means of a conditioning hyperpolarizing pulse at the level of control resting potential. The slope resistance increased gradually after maximum repolarization. The development of RAD in depolarized myocardium was associated with a time-dependent decrease in outward current (probably K current) and with increase in the background inward current, presumably flowing through the slow channel carrying Ca or Na ions, or both.