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

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 Ca 2+ currents (I Ca,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 I Ca,L , but the threshold potential of activation was significantly different among groups. Maximal I Ca,L responses to ISO were depressed in both experimental groups, but the EC 50 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 I Ca responses to ISO may be a result of a defect in β-adrenoceptor-AC pathway. Impairment of I Ca response in the excess group, however, appears to have a different underlying mechanism.