Role of external Ca2+ and K+ in gating of cardiac delayed rectifier K+ currents

We sought to determine whether extracellular Ca²⁺ (Ca_e²⁺) and K⁺ (K_e⁺) play essential roles in the normal functioning of cardiac K⁺ channels. Reports by others have shown that removal of Ca_e²⁺and K_e⁺alters the gating properties of neural delayed rectifier (I_K) and A-type K⁺ currents, resulting in a loss of normal cation selectivity and voltage-dependent gating. We found that removal of Ca_e²⁺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_e²⁺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.