Isoprenaline-evinced disturbances in action potentials from hearts of young cardiomyopathic hamsters

The electrophysiology of ventricular cells from prenecrotic stage 10 to 14 day old hamsters with hereditary cardiomyopathy (BIO 14.6 strain) was studied with the intent of learning more about the previously documented relationship of stimulation with beta-adrenergic agonist and the sarcolemmal defect contributing to the excessive uptake of calcium by diseased cells. Before catecholamine treatment only slight differences were observed in the configuration of action potentials of myopathics and control random bred hamsters (BIO RB strain). However, isoprenaline in varying concentrations, increased the action potential duration (APD) at 50% and 95% repolarisation levels to a significantly greater extent in myopathics than in controls. Repetition of the dose-response to isoprenaline in the presence of the beta-adrenergic antagonist propranolol (0.1 mumol X litre-1) permitted the calculation of the dissociation equilibrium constant for the antagonist. The similarity of dissociation constants between strains, 0.008 mumol X litre-1 for controls and 0.011 mumol X litre-1 for myopathics, suggests that a difference in interstrain receptor affinities is an unlikely cause of the isoprenaline effect. Rather, the data are more consistent with the hyper-sensitivity resulting from larger numbers of beta-adrenoceptors on sarcolemma of myopathic cells. Also, the increase in APD of myopathics indicates that isoproterenol elicits an imbalance of slow inward calcium and late outward potassium currents. The possible significance of the isoprenaline hyper-sensitivity, which is the earliest pathophysiology seen in this disease, to the etiology of cellular calcium overload and degeneration of diseased myocardium remains to be determined.