Platelet-activating factor receptor-dependent activation of the muscarinic K+ current in bullfrog atrial myocytes.
Platelet-activating factor (PAF), a potent signaling lipid implicated as a mediator of pathological responses, has both negative chronotropic and inotropic effects on the heart, although the mechanism(s) involved is not well defined. Because activation of the muscarinic acetylcholine-activated K+ current (IK(ACh)) also produces a negative chronotropic and inotropic response in myocardium, this study examines whether PAF has effects on IK(ACh) in isolated bullfrog atrial myocytes under whole-cell voltage-clamp conditions. We find that 2 microM PAF increases the rate of GTP-gamma-S-mediated IK(ACh) activation (from 0.30 +/- 0.01 min-1 [n = 20] to 0.73 +/- 0.07 min-1 [n = 12], p < 0.005, in the absence of acetylcholine). This effect of 2 microM PAF was blocked by the PAF antagonist CV-3988 (5 microM, 0.33 +/- 0.14 min-1 [n = 12]), suggesting the presence of specific PAF receptors coupled to IK(ACh) activation. Further support for mediation by specific G protein-coupled PAF receptors derives from the inability of PAF to modulate IK(ACh) after maximal activation in the presence of GTP-gamma-S. Eicosatetraynoic acid (ETYA, an inhibitor of 5- and 12-lipoxygenases) did not prevent the PAF-mediated increase in the rate of IK(ACh) activation (10 microM ETYA, 0.28 +/- 0.03 min-1 [n = 7]; 10 microM ETYA plus 2 microM PAF, 0.58 +/- 0.13 min-1 [n = 8]; p < 0.05), suggesting that the observed PAF effect is not mediated by increases in arachidonic acid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Ramos-Franco
J
J
Department of Physiology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205.
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Breitwieser
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D004553:Electric Conductivity; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D050356:Lipid Metabolism; D009116:Muscarine / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins; D011188:Potassium / Q000502:physiology*; D011892:Rana catesbeiana; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009116:Muscarine; D000109:Acetylcholine; D011188:Potassium