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D. A. Eisner^* and W. J. Lederer

University Laboratory of Physiology, Parks Road, Oxford OX1 3PT

1. Mammalian Purkinje fibres and ventricular muscle are significantly affected by exposure to low K solutions (Eisner & Lederer, 1979). Such exposure produces two 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 fibres 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 depolarizations and aftercontractions. The late effects in Purkinje fibres 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 `creep' in both current and tension.

2. The rate of development of early effects is consistent with the time taken to change the bathing K concentration, K_o. However 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 K_o.

3. The late effects of reducing K_o 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 K_o bathing solution. Similarly the late effects of 0 K_o, once established, can be reversed by adding these cations to the 0 K_o superfusing solution.

4. The order of potency of these cations to remove the effects of 0 K_o was found to be: Tl > K Rb > NH₄ Cs > Li. This is similar to the order of efficacy shown to activate the external K site of the Na pump in nerve and other tissue (Rang & Ritchie, 1968).

5. Strophanthidin (10^-5 M) produces qualitatively similar electrical and mechanical effects as those seen in 0 K_o. However, the effects of strophanthidin are not reversed by the activator cations. Furthermore, in the presence of strophanthidin (10^-5 M), these cations do not reverse the effects of 0 K_o.

6. In voltage-clamped Purkinje fibres, returning to a solution of 4 mM-K_o after exposure to 0 K_o produces a transient increase in outward current. Similarly, during exposure to 0 K_o 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 K_o.

7. The transient outward current produced by activator cations in 0 K_o is blocked by strophanthidin (10^-5 M). We conclude that the outward current transient reflects activation of an electrogenic Na pump. Furthermore, we find that, as in other tissues, the activator cations can substitute for K_o in activating the Na—K pump.

8. The reversal of inotropic and arrhythmogenic effects of 0 K_o by activator cations indicates that such effects result from Na pump blockade. No additional explanation (e.g. Ca/K exchange) need be invoked.

Present address: Department of Physiology, University of Maryland School of Medicine, 660 West Redwood Street, Baltimore, Maryland 21201, U.S.A.

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