Dietary Selenium and Vitamin E Intakes Alter β-Adrenergic Response of L-Type Ca-Current and β-Adrenoceptor-Adenylate Cyclase Coupling in Rat Heart

摘要

Previously we have shown that both insufficient (combined with vitamin E deficiency) and excess intake of selenium (Se) impairs isoproterenol (ISO)-induced contractions of rat papillary muscle. In the present study, we used patch-clamp and biochemical techniques to investigate mechanisms of this effect in rats fed a Se- and vitamin E-deficient, a Se-excess or a normal diet. Whole-cell configuration of patch-clamp technique was used to investigate l-type Ca2+ currents (ICa,L) and their regulation by β-adrenergic receptor stimulation in enzymatically isolated single rat ventricular myocytes. Alteration of Se and vitamin E intake did not affect peak ICa,L, but the threshold potential of activation was significantly different among groups. Maximal ICa,L responses to ISO were depressed in both experimental groups, but the EC50 values were not affected. In the Se-deficient group, basal, ISO- or forskolin-induced adenylate cyclase (AC) activity, measured in cardiac membrane preparations, was reduced when compared to the control, whereas 5′ guanylyimidodphosphate (GppNHp) stimulated activity was unaffected. Decreased β-adrenoceptor density and reduced GppNHp-induced affinity shift in ISO binding were also observed in the deficient group. No such differences were present in the excess group. These results suggest that combined Se and vitamin E deficiency interferes with β-adrenoceptor-AC coupling, whereas excess intake of Se does not affect it. Thus, in the deficient group, the impairment of ICa responses to ISO may be a result of a defect in β-adrenoceptor-AC pathway. Impairment of ICa response in the excess group, however, appears to have a different underlying mechanism.