Differential effects of d, l-sotalol and d-sotalol on isoproterenol-increased delayed rectifier outward potassium current in guinea pig single ventricular myocytes.
The aim of this study was to compare the effects of d, l-sotalol and d-Sotalol on the delayed rectifier K+ outward current in the presence of isoproterenol at different concentrations. Time-dependent delayed rectifier K+ outward currents were measured in isolated guinea pig single myocytes using the whole-cell configuration of the patch-clamp technique. Currents were measured in response to 300 ms depolarizing pulses from a holding potential of -40 mV in three experimental protocols [control, isoproterenol (10(-9) mol/L-10(-6) mol/L), and isoproterenol (10(-9) mol/L-10(-6) mol/L) plus either d, l-Sotalol (10(-4) mol/L) or d-Sotalol (10(-4) mol/L)]. IK tail currents were measured upon repolarization to -40 mV. It was found that IK was significantly amplified in the presence of isoproterenol (10(-9) mol/L-10(-6) mol/L) plus d-Sotalol. At 10(-8) mol/L isoproterenol, IK was increased by 92.7% +/- 17.1% (P < 0.05) and 54.3% +/- 13.4% after d-Sotalol addition (P < 0.05). In contrast, d, l-Sotalol completely conteracted the increase of Ik by isoproterenol (< 10(-8) mol/L), and compared to control, IK was decreased by 35.6% +/- 8.1% at 10(-8) mol/L isoproterenol plus d, l-Sotalol (P < 0.05). It is concluded that the beta-adrenergic blocking property of d, l-Sotalol but not that of d-Sotalol maintains the delayed rectifier K+ outward current blockade in the presence of isoproterenol in guinea pig myocytes. This might contribute to a superior antiarrhythmic efficacy as compared to d-Sotalol.
Yao
X
X
Department of Cardiology, University Hospital, Heidelberg University, Germany.
Yannoulis
N C
NC
Kiehn
J
J
Lu
Z
Z
Zhao
H
H
Brachmann
J
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D015221:Potassium Channels / Q000187:drug effects; D012032:Refractory Period, Electrophysiological; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D013015:Sotalol; D007545:Isoproterenol