Effects of (+)- and (+/-)-sotalol on repolarizing outward currents and pacemaker current in sheep cardiac Purkinje fibres.
This study was aimed to differentiate the action of (+)- and (+/-)-sotalol (10-1000 mumol/l) on membrane currents which are active during the repolarization of cardiac action potentials. Effects where studied in shortened sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique. Action potentials were activated at a frequency of 0.25 Hz and membrane currents at 0.03 Hz or 0.05 Hz in most experiments. Out of the currents investigated the transient outward current (ito) reacted most sensitively to (+)- and (+/-)-sotalol. Ito-amplitude was decreased on the average to 77% of reference at 10 mumol/l and to 53% at 1000 mumol/l (+)- or (+/-)-sotalol. The maximally available ito-current was decreased but the voltage-dependent control of inactivation was left nearly unchanged. The initial inwardly rectifying current (iK1), which propels the last repolarization phase of the action potential and controls resting potential to a large extent was reduced on the average to 93% of reference at 10 mumol/l and to 62% at 1000 mumol/l (+)- or (+/-)-sotalol. Time-dependent (delayed) outward current (iK) was on the average not affected by (+)- or (+/-)-sotalol up to 100 mumol/l and was decreased to 84% of reference current under the influence of 1000 mumol/l. An initial outward current, which is activated at positive membrane potentials (iinst) was not clearly affected by (+)- or (+/-)-sotalol at concentrations up to 1000 mumol/l. Pacemaker current (if) was not influenced by the drugs up to 100 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Berger
F
F
Institut für Pharmakologie der Universität Düsseldorf, Federal Republic of Germany.
Borchard
U
U
Hafner
D
D
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D011690:Purkinje Fibers / Q000187:drug effects*; D012756:Sheep; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism
D013015:Sotalol