Calcium-activated transient outward current in calf cardiac Purkinje fibres

Abstract

1. The possibility that the transient outward current of calf cardiac Purkinje fibres depends on intracellular calcium was investigated using a two micro-electrode voltage clamp. 2. Upon removal of Cao and replacement with Sr or Ba, the transient outward current was strongly suppressed. At the same time a large slow inward current was revealed. 3. Partial removal of Cao with replacement by Mg also diminished the transient outward current. The inhibition was not due to voltage shifts in the inactivation curve. 4. The kinetics of the peak transient outward current were compared with the kinetics of peak twitch force, an approximate measure of the level of Cai. The two signals were related in a linear manner during beat-dependent changes with trains of voltage clamp depolarizations. 5. Tension and transient outward current were also found to inactivate with a similar dependence on pre-potential and recover from inactivation along a similar time course. Both processes activated with membrane depolarization in a similar manner. 6. Intracellular injection of EGTA reduced the magnitude of the transient outward current and the twitch contraction. 7. The inhibition of outward current following EGTA injection was more pronounced for strong depolarizations. With pulses negative to - 10 mV, there was often little apparent change in the peak net outward current. 8. All lines of evidence support the hypothesis that the transient outward current is activated by intracellular Ca. 9. The functional significance of the transient outward current is discussed. Since a Ca-activated outward current would automatically offset slow inward Ca current, such a system may help prevent arrhythmogenic slow responses in the His-Purkinje network.