The mechanisms underlying the inotropic effect of reductions in [K⁺]_o were studied using recordings of membrane potential, membrane current, cell shortening and [Ca²⁺]_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 [Ca²⁺]_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 Ca²⁺ efflux via the sarcolemmal Na⁺–Ca²⁺ exchanger, Ca²⁺ influx via voltage‐dependant Ca²⁺ channels and sarcoplasmic reticulum (SR) Ca²⁺ 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.