Automatic Activity in Depolarized Guinea Pig Ventricular Myocardium: Characteristics and Mechanisms

Membrane potential was changed uniformly in segments, 0.7–1.0 mm long, of guinea pig papillary muscles exdsed from the right ventricle by using extracellular polarizing current pulses applied across two electrically insulated compartments. Rhythmic automatic depolarizations (RAD) occurred in 90% of preparations superfused with Tyrode's solution at maximum dlastolic 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 to 18.0 V/sec within a membrane potential range of -40 to + 20 mV. Raising extracellular Ca'+ concentration [Ca2+]n from 1.8 to 6.8 itim, or application of isoprotere-nol (10-5 g/ml) enhanced the rate of RAD, but lowering [CaJ+]0 to 0.4 mM or exposure to MnCl2 (6 mix) 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 ram, and in all fibers by raising [K+]o to 40.4 him. This suppression was dne 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 re polarization. These observations suggest that the development of RAD in depolarized myocardium is associated with a time-dependent decrease in outward current (probably K current) and with increase in the background inward current, presumably flowing through the stow channel carrying Ca or Na ions, or both.