PHYSIOLOGICAL-ROLE OF CA2+-ACTIVATED AND VOLTAGE-DEPENDENT K+ CURRENTS IN RABBIT CORONARY MYOCYTES

The properties and function of Ca2+-activated K+ (K-Ca) and voltage-dependent K+ (I-K) currents of rabbit coronary myocytes were studied under whole cell voltage-clamp conditions (22 degrees C). Inhibition of K-Ca by tetraethylammonium chloride (1-10 mM) or charybdotoxin (50-100 nM) suppressed noisy outward rectifying current elicited by 5-s voltage steps or ramp at potentials >0 mV, reduced the hump of the biphasic ramp current-voltage relation, and shifted by less than +5 mV the potential at which no net steady-state current is recorded (E(net); index of resting membrane potential). Inhibition of steady-state inward Ca2+ currents [I-Ca(L)] by nifedipine (1 mu M) displaced E(net) by -11 mV. Analysis of steady-state voltage dependence of I-K supported the existence of a ''window'' current between -50 and 0 mV. 4-Aminopyridine (2 mM) blocked a noninactivating component of I-K evoked between -30 and -40 mV, abolished the hump current during ramps, and shifted E(net) by more than +15 mV; hump current persisted during 2-min ramp depolarizations and peaked near the maximum overlap of the steady-state activation and inactivation curves of I-K (about -22 mV). A threefold rise in extracellu- lar Ca2+ concentration (1.8-5.4 mM) enhanced time-dependent outward K+ current (6.7-fold at + 40 mV) and shifted E(net) by -30 mV. It is concluded that, under steady-state conditions, I-K and I-Ca(L) play a major role in regulating resting membrane potential at a physiological level of intracellular Ca2+ concentration, with a minor contribution from K-Ca. However, elevation of intracellular Ca2+ concentration enhances K-Ca and hyperpolarizes the myocyte to limit Ca2+ entry through I-Ca(L).