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Dihydropyridine receptor binding sites in the cardiomyopathic hamster heart are unchanged from control
E Bazan1, M J Sole, A Schwartz
1Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575.
Insights
Calcium overload in cardiomyopathic hamster hearts may not stem from increased voltage-dependent calcium channels. Dihydropyridine receptor binding assays showed no significant difference in channel density, suggesting alternative causes for calcium overload.
Area of Science:
- Cardiovascular Research
- Molecular Cardiology
- Calcium Channel Biology
Background:
- Cardiac calcium overload is a hallmark of cardiomyopathy.
- Voltage-dependent calcium channels are potential contributors to this overload.
- Previous studies suggested an increased number of these channels in cardiomyopathic hearts.
Purpose of the Study:
- To investigate the density of dihydropyridine receptors, which represent voltage-dependent calcium channels, in the cardiac tissue of cardiomyopathic hamsters.
- To determine if an increased number of these channels correlates with observed calcium overload.
Main Methods:
- Radioligand binding assays using [3H]-(+)PN200110 to quantify dihydropyridine receptors.
- Analysis of cardiac muscle membranes from TO cardiomyopathic hamsters and age-matched controls.
- Comparison of binding parameters (Bmax and KD) between myopathic and control groups at different ages.
Main Results:
- No significant differences in the maximum binding capacity (Bmax) or dissociation constant (KD) for [3H]-(+)PN200110 were found in younger (35-41 days) cardiomyopathic hamsters compared to controls.
- Slight decreases in Bmax with no change in KD were observed in older (8-9 months) myopathic hamsters.
- These findings indicate no substantial increase in high-affinity dihydropyridine receptor density.
Conclusions:
- The calcium overload in cardiomyopathic hamster hearts is unlikely to be caused by an increased density of voltage-dependent calcium channels.
- The study suggests that other mechanisms may be responsible for the observed calcium dysregulation in this model of cardiomyopathy.
- Further research is needed to elucidate the precise molecular basis of calcium overload in this condition.
Abstract:
An increase in the number of voltage dependent calcium channels has been implicated in the overload of calcium found in cardiac tissue of the cardiomyopathic hamster. We examined the binding of [3H]-(+)PN200110 to dihydropyridine receptors in cardiac muscle membranes from TO cardiomyopathic hamsters. When compared to random bred controls, there were no differences in either the Bmax or the KD for [3H]-(+)PN200110 binding using homogenates from 35 to 41-day-old TO cardiomyopathic hearts. In 8 to 9-month-old myopathic animals there were only small decreases in Bmax with no change in KD. We suggest that the calcium overload observed in cardiomyopathic hamster heart may not be due to an increased density of calcium channels as estimated by high affinity dihydropyridine receptor binding sites.