title: Delayed rectifier outward K+ current is composed of two currents in guinea pig atrial cells.
abstract: The delayed rectifier outward K+ current (IK) was studied in isolated guinea pig atrial myocytes using the whole cell voltage-clamp technique. Similar to previous findings in ventricular cells, IK of atrial cells is the composite of two distinct components: IK,r, a rapidly activating current that exhibits strong inward rectification and IK,s, a slowly activating current with only modest rectification. IK,r was defined by its sensitivity to block by Co2+ and the class III antiarrhythmic agent, E-4031. IK,r underlies the prominent outward "hump" (between -30 and +40 mV) in the steady-state current-voltage relationship. Activation of IK,r was not dependent on transient changes in intracellular Ca2+ concentration. Block of Ca2+ current by nisoldipine or nitrendipine did not prevent activation of IK,r. Peak IK,r was not decreased in cells when intracellular Ca2+ was strongly buffered with 1,2-bis(aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. The activation curve for IK,r in atrial cells had a threshold of -40 mV, a half-point of -19 mV, and a slope factor of 5.2 mV. The activation curve for IK,s had a half-point of +24 mV and a slope factor of 15.7 mV. The peak tail currents of fully activated IK,s (21.1 pA/pF) and IK,r (2.53 pA/pF) are about two times that previously measured in guinea pig ventricular cells. This difference in current density may partly explain why action potentials of atrial cells are shorter than those of ventricular cells in guinea pig hearts.
authors.affiliation: Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 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; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002021:Buffers; D002118:Calcium / Q000037:antagonists & inhibitors / Q000502:physiology; D003035:Cobalt / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D007700:Kinetics; D009206:Myocardium / Q000166:cytology; D015737:Nisoldipine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D002021:Buffers; D010880:Piperidines; D011725:Pyridines; C063968:E 4031; D003035:Cobalt; D015737:Nisoldipine; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D011188:Potassium; D002118:Calcium