title: Involvement of A pertussis Toxin Sensitive G-Protein in the Inhibition of Inwardly Rectifying K Currents by Platelet-Activating Factor in Guinea-Pig Atrial Cardiomyocytes.
abstract: Platelet-activating factor (PAF) inhibits single inwardly rectifying K(+) channels in guinea-pig ventricular cells. There is currently little information as to the mechanism by which these channels are modulated. The effect of PAF on quasi steady-state inwardly rectifying K(+) currents (presumably of the I(K1) type) of auricular, atrial and ventricular cardiomyocytes from guinea-pig were studied. Applying the patch-clamp technique in the whole-cell configuration, PAF (10 nM) reduced the K(+) currents in all three cell types. The inhibitory effect of PAF occurred within seconds and was reversible upon wash-out. It was almost completely abolished by the PAF receptor antagonist BN 50730. Intracellular infusion of atrial cells with guanine 5'-(beta-thio)diphosphate (GDPS) or pretreatment of cells with pertussis toxin abolished the PAF dependent reduction of the currents. Neither extracellularly applied isoproterenol nor intracellularly applied adenosine 3',5'-cyclic monophosphate (cyclic AMP) attenuated the PAF effect. In multicellular preparations of auricles, PAF (10 nM) induced arrhythmias. The arrhythmogenic activity was also reduced by BN 50730. The data indicate that activated PAF receptors inhibit inwardly rectifying K(+) currents via a pertussis toxin sensitive G-protein without involvement of a cyclic AMP-dependent step. Since I(K1) is a major component in stabilizing the resting membrane potential, the observed inhibition of this type of channel could play an important role in PAF dependent arrhythmogenesis in guinea-pig heart.
authors.affiliation: Physiologisches Institut der Charité Humboldt-Universität zu Berlin Berlin 10115 Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gollasch
authors.forename: T
authors.initials: T
authors.lastname: Kleppisch
authors.forename: D
authors.initials: D
authors.lastname: Krautwurst
authors.forename: D
authors.initials: D
authors.lastname: Lewinsohn
authors.forename: J
authors.initials: J
authors.lastname: Hescheler