Effects of tetrodotoxin on electrical and mechanical activity of cardiac Purkinje fibers.

Canine Purkinje and ventricular muscle fibers were superfused in vitro and the actions of tetrodotoxin (TTX, 1.56 X 10(-5) - 3.2 X 10(-7) M) on both electrical and mechanical events were studied. Tetrodotoxin reduced the amplitude of the upstroke, markedly shortened the plateau, reduced the maximum diastolic potential and decreased contractile force in Purkinje fibers. Citrate (present in the TTX solution) did not have any effect on electrical and mechanical events. The modifications induced by TTX occurred whether external calcium concentration was normal, high or low. Furthermore, high calcium increased force by a similar extent whether TTX was present or not. TTX has little effect on slow action potentials due to the activation of the slow channel. Action potential duration and force were affected similarly by TTX as a function of concentration, of time of exposure and of rate of discharge. Also, TTX abolished action potentials due to a partially activated fast sodium current and reduced action potential duration and force much less in ventricular muscle than in Purkinje fibers. It is concluded that the effects of TTX are primarily related to a reduction of sodium influx during the action potential and that the fall in force is an indirect consequence of reduced sodium influx.