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)
Department of Physiology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205.
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Ramos-Franco
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Lo
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Breitwieser
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