DEPRESSION OF DELAYED OUTWARD K+ CURRENT BY CO2+ IN GUINEA-PIG VENTRICULAR MYOCYTES

Effects of Co2+ on the delayed outward K+ current (I(K)) in guinea pig ventricular myocytes were studied using the whole cell patch-clamp technique. I(K) was activated by depolarizing voltage pulses positive to -30 mV and reached half-maximal activation at +24 mV. Co2+ shifted the activation curve to a more depolarized voltage range in a concentration-dependent manner, with a Co2+ concentration at which half-maximal response occurs (IC50) of 8 mM and a saturation value of +38 mV. The voltage dependency of I(K) gatings showed a shift similar to that of activation. In both cases the shift could be explained by screening of surface potential. The density of total negative surface charges sensed by Co2+ was estimated to be 1 e/225 angstrom 2. Co2+ also reduced the fully activated I(K) [I(K(full))], and the dose-response curve had a Hill coefficient of 0.5 and an IC50 of 1 mM at 0 mV. Depression of I(K(full)) was mainly voltage independent. The single-channel unitary current estimated by fluctuation analysis was approximately 0.1 pA at -30 mV either in the absence or presence of Co2+. Therefore, the depression of I(K(full)) is due to an equivalent reduction in the number of functional channels. It is concluded that Co2+ depressed I(K) through multiple mechanisms.