Dose-dependent alteration of rat cardiac sodium current by isoproterenol: Results from direct measurements on multicellular preparations
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Conflicting results have been reported in literature about the influence ofβ-adrenergic stimulation on the fast cardiac sodium current (INa+). To elucidate these mechanisms in multicellular preparations we used the loose-patch-clamp technique to evaluate the effect of theβ-adrenergic agonist isoproterenol 1–1000 nmol/l. Isoproterenol enhancedINa+ at all membrane potentials by elevation of the maximal availableINa+. Only at the high concentration of 1 μmol/l wasINa+ slightly depressed after depolarizing conditioning clamps. The most marked increase of the maximal availableINa+ was 30 ± 9 % after application of 100 nmol/l isoproterenol. To learn about the mechanisms in view of sodium channel modulation we combined isoproterenol with the sodium channel blocker lidocaine (47 μmol/l). Under these circumstances the effects of both drugs were completely independent. This investigation shows clearly that low concentrations of isoproterenol increaseINa+ in multicellular preparations by a gating-independent mechanism.
Key wordsSodium current Adrenergic regulation Loose-patch-clamp Rat papillary muscle
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