title: Mechanism of the membrane depolarization induced by oxidative stress in guinea-pig ventricular cells.
abstract: Mechanism of the membrane depolarization induced by oxidative stress was examined using ion-selective microelectrode and patch clamp techniques. In guinea-pig papillary muscles stimulated at 0.5 Hz, cumene hydroperoxide (CH) at a concentration of 300 microM decreased the resting membrane potential and shortened the action potential, concomitantly with muscle contracture. The membrane depolarization was not associated with a significant decrease in intracellular potassium ion activity, indicating that the depolarization is not due to a decrease in potassium equilibrium potential resulting from leak of intracellular K+. In isolated guinea-pig ventricular cells. CH (10-30 microM) consistently decreased the inward rectifier potassium current and slightly decreased the calcium current. In cell-attached patches CH inhibited the opening of the inward rectifier K+ channel without affecting the unit amplitude of the single channel current. Thus, the depolarization of the resting membrane induced by oxidative stress is, at least in part, due to the inhibition of the inward rectifier K+ channel activity, and may play an important role in the genesis of reperfusion-induced arrhythmias.
authors.affiliation: Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakaya
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.forename: N
authors.initials: N
authors.lastname: Tohse
authors.forename: M
authors.initials: M
authors.lastname: Kanno
mesh_terms: D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology
chemical_list: D001555:Benzene Derivatives; D015221:Potassium Channels; C007164:cumene hydroperoxide; D010100:Oxygen