title: Role of external Ca2+ and K+ in gating of cardiac delayed rectifier K+ currents.
abstract: We sought to determine whether extracellular Ca2+ (Ca2+e) and K+ (K+e) play essential roles in the normal functioning of cardiac K+ channels. Reports by others have shown that removal of Ca2+e and K+e alters the gating properties of neural delayed rectifier (IK) and A-type K+ currents, resulting in a loss of normal cation selectivity and voltage-dependent gating. We found that removal of Ca2+e 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 IK. The effect of [K+]e on the magnitude of the two components of cardiac IK was also examined. IK in guinea pig myocytes is comprised of two distinct types of currents: IKr (rapidly activating, rectifying) and IKs (slowly activating). The differential effect of Ca2+e on the two components of IK (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 IKs and IKr. Lowering [K+]e from 4 to 0 mM increased IKs, as expected from the change in driving force for K+, but decreased IKr. The differential effect of [K+]e on the two components of cardiac IK may explain the reported discrepancies regarding modulation of cardiac IK conductance by this cation.
authors.affiliation: Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
authors.forename: M C
authors.initials: MC
authors.lastname: Sanguinetti
authors.forename: N K
authors.initials: NK
authors.lastname: Jurkiewicz
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D005110:Extracellular Space / Q000502:physiology*; D006168:Guinea Pigs; D015640:Ion Channel Gating; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology
chemical_list: D015221:Potassium Channels; D011188:Potassium; D002118:Calcium