Effect of Tetrodotoxin on Membrane Currents in Mammalian Cardiac Fibres

Abstract

THE action potential of cardiac fibres differs from that of most other cell types: the fast rising phase is followed by a plateau lasting a few 100 msec. The results of voltage clamp analysis in Purkinje fibres¹ show that a depolarizing voltage step elicits a large sodium current, which has a slow component which declines for several hundred milliseconds. The potassium current falls after depolarization with a similar time constant. The slow decline of both currents can explain the plateau of the cardiac action potential. The sodium current was identified by comparing the membrane currents in Tyrode solution with those in a sodium-free solution¹. An independent check of this procedure would be useful; we therefore investigated the effect of tetrodotoxin (TTX) on short Purkinje fibres of sheep. TTX at concentrations of 10⁻⁸ to 10⁻⁷ g/ml. is known to block selectively the excitatory inward sodium current in invertebrate axons^2,3. We recorded membrane potentials in fourteen preparations and passed current through a second intracellular glass microelectrode. Details of the preparation and of the electronic apparatus are given elsewhere⁴.