Changes in extracellular K+ concentration modulate contractility of rat and rabbit cardiac myocytes via the inward rectifier K+ current IK1.

The mechanisms underlying the inotropic effect of reductions in [K(+)](o) were studied using recordings of membrane potential, membrane current, cell shortening and [Ca(2+)](i) in single, isolated cardiac myocytes. Three types of mammalian myocytes were chosen, based on differences in the current density and intrinsic voltage dependence of the inwardly rectifying background K(+) current I(K1) in each cell type. Rabbit ventricular myocytes had a relatively large I(K1) with a prominent negative slope conductance whereas rabbit atrial cells expressed much smaller I(K1), with little or no negative slope conductance. I(K1) in rat ventricle was intermediate in both current density and slope conductance. Action potential duration is relatively short in both rabbit atrial and rat ventricular myocytes, and consequently both cell types spend much of the duty cycle at or near the resting membrane potential. Rapid increases or decreases of [K(+)](o) elicited significantly different inotropic effects in rat and rabbit atrial and ventricular myocytes. Voltage-clamp and current-clamp experiments showed that the effects on cell shortening and [Ca(2+)](i) following changes in [K(+)](o) were primarily the result of the effects of alterations in I(K1), which changed resting membrane potential and action potential waveform. This in turn differentially altered the balance of Ca(2+) efflux via the sarcolemmal Na(+)-Ca(2+) exchanger, Ca(2+) influx via voltage-dependant Ca(2+) channels and sarcoplasmic reticulum (SR) Ca(2+) release in each cell type. These results support the hypothesis that the inotropic effect of alterations of [K(+)](o) in the heart is due to significant non-linear changes in the current-voltage relation for I(K1) and the resulting modulation of the resting membrane potential and action potential waveform.