Low Ba-induced pacemaker current in well-polarized cat papillary muscle

Abstract

It has previously been reported that superfusion of normally quiescent mammalian ventricular muscle with low concentrations of Ba (less than 0.3 mM) can induce spontaneous activity with maximum diastolic potentials (MDP) that are similar to the normal resting potential (-80 mV or larger). The mechanism for this activity was studied in cat papillary muscle sucrose-gap preparations under current clamp and voltage-clamp conditions. Hyperpolarizing current pulses decreased or abolished the amplitude of the pacemaker potential in a voltage-dependent manner. When Ba concentration was increased to 2 mM the MDP depolarized by approximately 20 mV. Hyperpolarizing steps under these conditions abolished the diastolic depolarization, also in a voltage-dependent manner. Voltage clamping the preparation at the MDP during superfusion of 0.2 mM Ba revealed a time-dependent, inwardly directed current. Hyperpolarizing voltage-clamp steps from a holding potential of -50 mV showed that this current was maximal at approximately -70 mV and frequently reversed at membrane potentials of approximately -95 to -115 mV. The time course of this current was biexponential, and the time constant of the faster component decreased with larger hyperpolarization. When the same voltage-clamp protocol was repeated in the presence of 2 mM Ba, no time-dependent current change was detected. In four out of five experiments, Cs (2.5 mM) reduced (but never abolished) the amplitude of the low Ba-induced current. Our results do not support the hypothesis that a hyperpolarization-induced current (iF-like current) is responsible for the automaticity in well-polarized ventricular muscle at low Ba concentrations. Instead, our data suggest that this pacemaker activity is the result of a Ba-induced, time-dependent blockade of the inward rectifier potassium current (iK1).