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Calcium antagonist binding sites in failing and nonfailing human ventricular myocardium
R P Rasmussen1, W Minobe, M R Bristow
1Division of Cardiology, University of Utah School of Medicine, Salt Lake City 84132.
Insights
In human idiopathic dilated cardiomyopathy, the number of calcium channels did not significantly change, contrary to findings in hamsters. This suggests calcium channel density is not a key factor in this specific heart failure condition.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Studies in myopathic hamsters suggest increased calcium antagonist binding sites, potentially leading to calcium overload and myocardial damage.
- Idiopathic dilated cardiomyopathy is a severe heart condition where understanding calcium channel dynamics is crucial.
Purpose of the Study:
- To investigate whether calcium antagonist binding sites are increased in human idiopathic dilated cardiomyopathy.
- To test the hypothesis that altered calcium channel numbers contribute to the pathophysiology of this heart condition.
Main Methods:
- Examined [3H]PN 200-110 and [3H]nitrendipine binding in heart membranes from nonfailing controls and patients with idiopathic dilated cardiomyopathy.
- Measured beta receptor density to assess overall receptor changes in failing hearts.
Main Results:
- Beta receptor density was significantly decreased by 50% in failing hearts.
- Dihydropyridine calcium antagonist binding sites ([3H]PN 200-110 and [3H]nitrendipine) were not significantly altered in idiopathic dilated cardiomyopathy ventricles compared to nonfailing controls.
- Dissociation constants (KD) for the calcium antagonists were similar in both failing and nonfailing hearts.
Conclusions:
- Dihydropyridine calcium antagonist binding sites are not significantly altered in the failing human left ventricle with idiopathic dilated cardiomyopathy.
- The increase in calcium channels observed in myopathic hamsters does not appear to translate to human idiopathic dilated cardiomyopathy.
Abstract:
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.