The role of the sodium pump in the effects of potassium‐depleted solutions on mammalian cardiac muscle

Abstract

Mammalian [guinea pig] Purkinje fibers and ventricular muscle are significantly affected by exposure to low K solutions. Such exposure produces 2 classes of effects. Early effects, developing over tens of seconds include (in ventricular muscle) a more negative resting potential and a lengthening of the action potential. In Purkinje fibers the principal early effect is a decrease in slope conductance. Late effects develop over minutes. In ventricular muscle such effects include a shortening of the action potential, an increase in twitch and tonic tension and the development of transient depolarization and aftercontractions. The late effects in Purkinje fibers are the increase in twitch tension and voltage dependent tonic tension, the development of transient depolarizations and the underlying oscillatory transient inward currents, the appearance of aftercontractions accompanying the transient depolarizations or transient inward currents, and the development of a slow crrep in both current and tension. The rate of development of early effects is consistent with the time taken to change the bathing K concentration, Ko. the time course of onset of the late effects (including the positive inotropy) is too slow to be explained by the time taken to change Ko. The late effects of reducing Ko from 4 to 0 mM can be prevented by including appropriate concentrations of the activator cations of the Na pump (Tl, Rb, Cs, NH4 or Li) in the 0 Ko bathing solution. The late effects of 0 Ko, once established, were reversed by adding these cations to the 0 Ko superfusing solution. The order of potency of these cations to remove the effects of 0 Ko was Tl > K .simeq. Rb > NH4 .simeq. Cs > Li. This is similar to the order of efficacy that activates the external K site of the Na pump in nerve and other tissue. Strophanthidin (10-5 M) produces qualitatively similar electrical and mechanical effects as those seen in 0 Ko. The effects of strophanthidin are not reversed by the activator cations. In the presence of strophanthidin (10-5 M), these cations do not reverse the effects of 0 Ko. In voltage-clamped Purkinje fibers, returning to a solution of 4 mM-Ko after exposure to 0 Ko produces a transient increase in outward current. During exposure to 0 Ko the addition of activator cations also produces a transient increase of outward current. The ability of these ions to develop this outward transient current is correlated with their ability to remove the inotropic and arrhythmogenic effects of 0 Ko. The transient outward current produced by activator cations in 0 Ko is blocked by strophanthidin (10-5 M). The transient outward current reflects activation of an electrogenic Na pump. As in other tissues, the activator cations can substitute for Ko in activating the Na-K pump. The reversal of inotropic and arrhythmogenic effects of 0 Ko by activator cations indicates that such effects result from Na pump blockade. No additional explanation (e.g., Ca/K exchange) need be invoked.