Cellular electrophysiological effects of platelet-activating factor (PAF) and its antagonist BN 52021 in cardiac preparations.
The effects of PAF and its antagonist BN 52021 were studied on the transmembrane action potential (AP) in atrial and ventricular papillary muscles of guinea-pig. PAF (10(-11)-10(-7) M) did not modify the resting membrane potential (RP) nor the maximum rate of depolarization (Vmax) either in atrial or in ventricular fibres. At 10(-11) M, PAF increased the amplitude of AP both in atrial and ventricular muscles. the repolarization phase was dose-dependently shortened in the case of atrium, while the duration of ventricular AP was somewhat increased. The K+ channel blocker 4-aminopyridine (10(-3) M) prevented the effect of PAF on the duration of atrial AP. BN 52021 (10(-7) M to 10(-5) M) produced a significant shortening of the duration of atrial AP and did not modify the other parameters. In papillary muscle up to 10(-6) M, it increased both RP and the amplitude of AP and caused a dose-dependent shortening of the repolarization. Neither PAF (10(-11) to 10(-7) M) nor BN 52021 (10(-5) M) was able to induce slow AP in guinea-pig atrial and ventricular preparations depolarized by 25 mM K+ Tyrode solution. PAF did not modify the slow AP elicited by isoprenaline (5 x 10(-7) M). The present findings suggest that neither PAF nor BN 52021 affects slow inward Ca2+ current but their effects on other ionic currents, e.g. K+ currents, may be important.
Kecskemeti
V
V
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
Braquet
P
P
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides; D006168:Guinea Pigs; D007783:Lactones / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D015221:Potassium Channels; D015761:4-Aminopyridine; C045856:ginkgolide B; D002118:Calcium