Calcium antagonist binding sites in failing and nonfailing human ventricular myocardium.

Studies in myopathic hamsters have described an increase in calcium antagonist binding sites, which is presumably associated with an increase in the number of calcium channels. Such an abnormality might predispose the heart to further myocardial damage from calcium overload. We tested the hypothesis that calcium antagonist binding sites are increased in human idiopathic dilated cardiomyopathy by examining [3H]PN 200-110 and [3H]nitrendipine binding in membranes prepared from nonfailing controls and severely failing ventricles with idiopathic dilated cardiomyopathy. Despite the fact that beta receptor density was decreased by 50% in failing hearts (iodocyanopindolol Bmax 84.4 +/- 8.9 fmol/mg protein in nonfailing hearts vs 42.9 +/- 3.2 fmol/mg in failing hearts, P less than 0.01), dihydropyridine calcium antagonist binding sites were not reduced significantly by heart failure. Maximum binding of [3H]PN 200-110 was 92.9 +/- 19.4 fmol/mg protein in membranes derived from failing ventricles, and 93.5 +/- 17.4 fmol/mg in membranes derived from nonfailing ventricles (P = NS); values for [3H]nitrendipine maximum binding were similar to those for [3H]PN 200-110 and also were not reduced significantly in failing ventricles. Additionally, the dissociation constants (KD) for [3H]nitrendipine and [3H]PN 200-110 were not significantly different in failing and nonfailing heart. We conclude that dihydropyridine calcium antagonist binding sites are not altered significantly in the failing human left ventricle with idiopathic dilated cardiomyopathy.