Effects of (+)- and (+/-)-sotalol on repolarizing outward currents and pacemaker current in sheep cardiac Purkinje fibres

Abstract

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)