We sought to determine whether extracellular Ca2+ (Ca(e)2+) and K+ (K(e)+) play essential roles in the normal functioning of cardiac K+ channels. Reports by others have shown that removal of Ca(e)2+ and K(e)+ alters the gating properties of neural delayed rectifier (I(K)) and A-type K+ currents. resulting in a toss of normal cation selectivity and voltage-dependent gating. We found that removal of Ca(e)2+ and K(e)+ from the solution bathing guinea pig ventricular myocytes often induced a leak conductance, but did not affect the ionic selectivity or time-dependent activation and deactivation properties of I(K). The effect of [K+]e on the magnitude of the two components of cardiac I(K) was also examined. I(K) in guinea pig myocytes is comprised of two distinct types of currents: I(Kr), (rapidly activating, rectifying) and I(Ks) (slowly activating). The differential effect of Ca(e)2+ on the two components of I(K) (previously shown to shift the voltage dependence of activation of the two currents in opposite directions) was exploited to determine the role of K(e)+ on the magnitude of I(Ks) and I(Kr). Lowering [K+]e from 4 to 0 mM increased I(Ks), as expected from the change in driving force for K+, but decreased I(Kr). The differential effect of [K+]e on the two components of cardiac I(K) may explain the reported discrepancies regarding modulation of cardiac I(K) conductance by this cation.
