Binding of A 1,4-dihydropyridine calcium channel activator, (-) S Bay K 8644, to cardiac preparations.
The 1,4-dihydropyridine Ca2+ channel activator, (-) [3H]Bay K 8644, binds to cardiac membranes and polarized [5 mM K+] and depolarized [50 mM K+] cardiac cells. Binding to microsomal membranes at 25 degrees C indicates a single set of binding sites, KD = 2.9 x 10(-9) M and a site density, 337 fmoles/mg protein, not different from that measured by antagonist 1,4-dihydropyridines. Binding to neonatal rat myocytes at 37 degrees C was independent of membrane potential with a KD value of 5 x 10(-8)M and a site density, 63 fmoles/mg protein, not significantly different from that measured by PN 200 110. These results indicate that 1,4-dihydropyridine activators and antagonists label the same number of binding sites in cardiac tissue, but that activator binding to intact myocytes is voltage-independent.
Ferrante
J
J
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
Luchowski
E
E
Rutledge
A
A
Triggle
D J
DJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014316:Tritium
D015220:Calcium Channels; D011978:Receptors, Nicotinic; D014316:Tritium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester