Effect of tetrodotoxin on the inward ionic current the guinea pig atrium

SUMMARY The inward ionic current in the atrium has been measured by electronic differentiation of the voltage, time signal, on the assumption that the single cell penetrated by the micro-electrode shows cable-like properties. The method exploits fully information contained in the upstroke of the action potential, and an internally consistent set of parameters can be derived. Tetrodotoxin was found to reduce the fast inward ionic current, and to shift the voltage of maximum current flow to more negative values. TTX augmented the effects of high stimulation rates but did not alter the refractory period of the atrium. It is suggested that TTX interacts with the Na+ channel so as to reduce activation of the Na+ current and hence unit conductance. The present results are consistent with the apparent voltage-dependence of TTX action, since activation and inactivation of the Na+ current are both voltage-sensitive phenomena. The pharmacologist who wishes to examine the effects of drugs on the electrophysiological properties of cardiac tissue is faced with the problem of obtaining data to characterise adequately the behaviour of the fast inward membrane current. Considerable difficult