Involvement of A pertussis Toxin Sensitive G-Protein in theInhibition of Inwardly Rectifying K+Currents byPlatelet-Activating Factor in Guinea-Pig Atrial Cardiomyocytes

[摘要] Platelet-activating factor (PAF) inhibits single inwardly rectifyingK+channels in guinea-pig ventricular cells. Thereis currently little information as to the mechanism by which thesechannels are modulated. The effect of PAF on quasi steady-stateinwardly rectifying K+currents (presumably of theIK1type) of auricular, atrial and ventricular cardiomyocytes fromguinea-pig were studied. Applying the patch-clamp technique in thewhole-cell configuration, PAF (10 nM) reduced the K+currents in all three cell types. The inhibitory effect of PAFoccurred within seconds and was reversible upon wash-out. It wasalmost completely abolished by the PAF receptor antagonist BN 50730.Intracellular infusion of atrial cells with guanine5′-(β-thio)diphosphate (GDPS) or pretreatment of cellswith pertussis toxin abolished the PAF dependent reduction of thecurrents. Neither extracellularly applied isoproterenol norintracellularly applied adenosine 3′,5′-cyclicmonophosphate (cyclic AMP) attenuated the PAF effect. Inmulticellular preparations of auricles, PAF (10 nM) inducedarrhythmias. The arrhythmogenic activity was also reduced by BN50730. The data indicate that activated PAF receptors inhibitinwardly rectifying K+currents via a pertussistoxin sensitive G-protein without involvement of a cyclicAMP-dependent step. Since IK1is a major component instabilizing the resting membrane potential, the observed inhibitionof this type of channel could play an important role in PAFdependent arrhythmogenesis in guinea-pig heart.

[学科分类] 生理学与病理学