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Article

Dietary Selenium and Vitamin E Intakes Alter ß-Adrenergic Response of L-Type Ca-Current and ß-Adrenoceptor-Adenylate Cyclase Coupling in Rat Heart¹

Kemal Sayar^*, Mehmet Ugur, Hakan Gürdal^*, Ongun Onaran^*, Omer Hotomaroglu and Belma Turan²

Faculty of Medicine, Departments of ^* Pharmacology and Clinical Pharmacology, Biophysics, Sihhiye 06100, Ankara University, Ankara, Turkey

²To whom correspondence should be addressed.

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 (I_Ca,L) and their regulation by ß-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 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 ß-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 ß-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 ß-adrenoceptor-AC pathway. Impairment of I_Ca response in the excess group, however, appears to have a different underlying mechanism.

KEY WORDS: • trace element • selenium • vitamin E • receptor-adenylate cyclase coupling • rat cardiac myoctes