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

We have investigated the electrical and mechanical effects of reducing the bathing K concentration, K(o), over the range from 4-0 mM in guinea pig papillary muscle and in sheep Purkinje fibres. In papillary muscle, reducing K(o) to zero 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. Finally, transient depolarizations and aftercontractions are produced. In voltage clamped Purkinje fibres, K(o) reduction decreases the slope conductance at the more negative potentials and reduces the pace-maker current, i(K)2. Twitch tension increases rapidly and voltage dependent tonic tension develops. After even very short exposures to very low K(o) (1 mM and below), an oscillatory 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 by Kass, Lederer, Tsien & Weingart (1978). Prolonged exposure to O K(o) leads to the development of a slow current 'creep'. This current is activated by depolarization and has a reversal potential of -6.7 ± 3.5mV. 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 still similar to each other. Fluctuations appear in both the tension and current records during exposure to low K(o). The tension and current fluctuations have similar principal frequencies (about 1 Hz). Ca(o) removal, substituting Ba(o) for Ca(o) or adding Mn(o) (2 mM) can each remove the transient inward current, aftercontraction, fluctuations of current and tension, and creep current as well as the increase of twitch and tonic tension. Replacing Ca(o) by Sr(o) leads to an increased inotropic effect of low K(o) with altered kinetics and appears to abolish the transient inward current, aftercontraction and fluctuations of current and tension.