Comparison of the sodium currents in normal Purkinje fibres and Purkinje fibres surviving infarction - A pharmacological study

Abstract

1. Purkinje fibres surviving infarction showed a lower maximum upstroke velocity (V̇(max)) and a longer action potential duration when compared to normal Purkinje fibres. A reduction in the fast sodium current and an increase in the sodium 'window' current may be responsible for the observed alterations in V̇(max) and action potential duration respectively. 2. Since voltage clamp studies were not feasible, a pharmacological approach was used. The responses to tetrodotoxin (TTX) and lignocaine in normal Purkinje fibres and Purkinje fibres surviving infarction were used to examine the sodium currents in these fibres. 3. V̇(max), an indirect measure of the fast sodium current, was more sensitive to lignocaine in Purkinje fibres surviving infarction than in normal Purkinje fibres. The reduction in V̇(max) by lignocaine was more prominent at the shorter stimulation cycle length. Significant reduction of V̇(max) was observed with the higher concentration of TTX and no differential effect on V̇(max) between normal Purkinje fibres and Purkinje fibres surviving infarction was detected. 4. Reduction of action potential duration in the presence of TTX or lignocaine was used as a measure of the sodium 'window' current. A greater reduction of action potential duration by TTX and lignocaine was observed in normal Purkinje fibres than in Purkinje fibres surviving infarction. 5. The results suggested that the fast sodium current in Purkinje fibres surviving infarction is more sensitive to pharmacological agents with local anaesthetic properties and the prolonged action potential duration in these Purkinje fibres cannot be due to an increase in the sodium 'window' current. The results are compatible with an enhanced effect of antiarrhythmic drugs on V̇(max) and conduction in the ischaemic heart.