Voltage dependence of Na/K pump current in isolated heart cells

Abstract

The Na/K pump usually pumps more Na⁺ out of the cell than K⁺ in, and so generates an outward component of membrane current^1,2 which, in the heart, can be an important modulator of the frequency and shape of the cardiac impulse^3–5. Because it is electrogenic, Na/K pump activity ought to be sensitive to membrane potential, and it should decline with hyperpolarization^6–9. However, such voltage dependence of outward pump current has yet to be demonstrated^6–10, one reason being the technical difficulty of accurately measuring pump current over a sufficiently wide voltage range. The whole-cell patch-clamp technique¹¹ allows effective control of both intracellular and extracellular solutions as well as membrane voltage. Applying this technique to myocardial cells isolated from guinea pig ventricle, we have measured Na/K pump current between −140 mV and +60 mV, after minimizing passive currents flowing through Ca²⁺, K⁺ and Na⁺ channels. We report here that strongly activated pump current shows marked voltage dependence; it declines steadily from a maximal level near 0 mV, becoming very small at −140 mV. Pump current–voltage relationships will provide essential information for testing models of the Na/K pump mechanism and for predicting pump-mediated changes in the electrical activity of excitable cells.