Inotropic and arrhythmogenic effects of potassium‐depleted solutions on mammalian cardiac muscle.

Abstract

The electrical and mechanical effects of reducing the bathing K concentration, Ko, were studied over the range from 4-0 mM in guinea pig papillary muscle and in sheep Purkinje fibers. In papillary muscle, reducing Ko to 0 produces a negative shift in the resting potential and an initial increase in action potential duration. An increase of twitch tension ensues, followed by a reduction in action potential duration and, eventually, an increase in tonic tension. This increase in tonic tension is often accompanied by a decrease of twitch tension. Transient depolarizations and aftercontractions are produced. In voltage clamped Purkinje fibers, Ko reduction decreases the slope conductance at the more negative potentials and reduces the pacemaker current, iK2. Twitch tension increases rapidly and voltage dependent tonic tension develops. After even very short exposures to very low Ko (1 mM and below), an osciallatory transient inward current and accompanying aftercontraction can be seen. The oscillatory transient inward current and aftercontraction are similar to those described for cardiotonic steroid intoxication. Prolonged exposure to 0 Ko leads to the development of a slow current creep. This current is activated by depolarization and has a reversal potential of -6.7 .+-. 3.6 mV. The development of this creep current is accompanied by an increasing creep in tonic tension with the same time course. On repolarization both the current creep and creep in tension recover with time courses similar to each other. Fluctuations appear in both the tension and current records during exposure to low Ko. the tension and current fluctuations have similar principal frequencies (about 1 Hz). Cao removal, substituting Bao for Cao or adding Mno (2 mM) can each remove the transient inward current, aftercontraction, fluctuations of current and tension, creep current and the increase of twitch and tonic tension. Replacing Cao by Sro causes an increased inotropic effect of low Ko with altered kinetics and appears to abolish the transient inward current, aftercontraction and fluctuations of current and tension. Cai [intracellular Ca] plays a central role in the inotropic and arrhythmogenic effects of low Ko. Possible mechanisms of Cai control are discussed.