title: Depression of delayed outward K+ current by Co2+ in guinea pig ventricular myocytes.
abstract: Effects of Co2+ on the delayed outward K+ current (IK) in guinea pig ventricular myocytes were studied using the whole cell patch-clamp technique. IK 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 IK 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 A2. Co2+ also reduced the fully activated IK [IK(full)], and the dose-response curve had a Hill coefficient of 0.5 and an IC50 of 1 mM at 0 mV. Depression of IK(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 IK(full) is due to an equivalent reduction in the number of functional channels. It is concluded that Co2+ depressed IK through multiple mechanisms.
authors.affiliation: Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
authors.forename: Z
authors.initials: Z
authors.lastname: Fan
authors.forename: M
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: D000818:Animals; D003035:Cobalt / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology
chemical_list: D015221:Potassium Channels; D003035:Cobalt; D011188:Potassium