On the mechanisms of action of PAF on the myocardium.
The effects of PAF (1-2 X 10(-7) M) on intracellular slow Ca-mediated action potentials (Ca-AP) and isometric contractions of guinea-pig auricle muscles and ionic currents of frog atrial trabeculae were investigated. PAF decreased the amplitude, duration and upstroke velocity of the slow Ca-AP mediated via the L-type Ca channels in guinea-pig auricle muscles without changes in the resting potential. The PAF receptor antagonist U-66985 (1-5 X 10(-6) M), histamine (10(-4) M) and 4-aminopyridine (3 mM) inhibited the depressant effects of PAF on the slow AP and contractions. PAF reduced the peak of the slow inward Ca current (ICa) via the L-type Ca channels of frog atrial trabeculae. Simultaneously, the delayed outward K current (IK) was increased by PAF. Pretreatment with the PAF receptor antagonist BN 52021 (4 X 10(-6) M) protected the effects of PAF on ICa and IK. Our data demonstrate both by direct and indirect methods of ICa registration an inhibiting effect of PAF on the ICa via the L-type Ca channels and make probable a similarity in PAF signalling in cardiac cells of cold- and warm-blooded animals. The coupling of changes of the ICa with the augmentation of IK accentuate the important role of myocardial L-type Ca and K channels in mediating the negative inotropic action of PAF. The ability of U-66985 and BN 52021 to inhibit the electrophysiological effects of PAF hint at a membrane signalling coupled by specific binding sites for PAF in the myocardium.
Gollasch
M
M
Institute of Physiology, Humboldt-University, Berlin, Germany.
Ignatieva
V B
VB
Kobrinsky
E M
EM
Vornovitsky
E G
EG
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D004224:Diterpenes; D046934:Ginkgolides; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011895:Rana ridibunda
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D006632:Histamine; C046779:U 66985; D015761:4-Aminopyridine; C045856:ginkgolide B; D002118:Calcium