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 influence of beta-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 the beta-adrenergic agonist isoproterenol 1-1000 nmol/l. Isoproterenol enhanced INa+ at all membrane potentials by elevation of the maximal available INa+ . Only at the high concentration of 1 micromol/l was INa+ slightly depressed after depolarizing conditioning clamps. The most marked increase of the maximal available INa+ 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 micromol/l). Under these circumstances the effects of both drugs were completely independent. This investigation shows clearly that low concentrations of isoproterenol increase INa+ in multicellular preparations by a gating-independent mechanism.
Kirstein
M
M
Medical University Clinic, Josef-Schneider-Strasse 2, D-97080 Würzburg; Germany.
Eickhorn
R
R
Kochsiek
K
K
Langenfeld
H
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D008012:Lidocaine / Q000494:pharmacology; D010210:Papillary Muscles / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D008012:Lidocaine; D007545:Isoproterenol