DOSE-DEPENDENT ALTERATION OF RAT CARDIAC SODIUM CURRENT BY ISOPROTERENOL - RESULTS FROM DIRECT MEASUREMENTS ON MULTICELLULAR PREPARATIONS

Conflicting results have been reported in literature about the influen ce of beta-adrenergic stimulation on the fast cardiac sodium current ( I-Na+). To elucidate these mechanisms in multicellular preparations we used the loose-patch-clamp technique to evaluate the effect of the be ta-adrenergic agonist isoproterenol 1-1000 nmol/1. Isoproterenol enhan ced I-Na+ at all membrane potentials by elevation of the maximal avail able I-Na+. Only at the high concentration of 1 mu mol/1 was I-Na+ sli ghtly depressed after depolarizing conditioning clamps. The most marke d increase of the maximal available I-Na+ was 30 +/- 9% after applicat ion of 100 nmol/1 isoproterenol. To learn about the mechanisms in view of sodium channel modulation we combined isoproterenol with the sodiu m channel blocker lidocaine (47 mu mol/1). Under these circumstances t he effects of both drugs were completely independent. This investigati on shows clearly that low concentrations of isoproterenol increase I-N a+ in multicellular preparations by a gating-independent mechanism.