Abstract

Mouse neuroblastoma N-18 cells, which evoked a mixed Na⁺ and Ca²⁺ action potential under appropriate tissue culture conditions, were used to study the electrophysiological pharmacology of a polypeptide neurotoxin (ATX-II) from a sea anemone. When applied extracellularly, ATX-II in concentrations as low as 10^-7 M increased reversibly the electrical excitability of N-18 cells, e.g., the toxin caused spontaneous firing in which the duration and the maximal rate of rise of each action potential were increased. A set of results obtained in this work strongly suggests that this effect of the toxin was mainly due to its interaction with the inactivation gate of the Na⁺ channel of N-18 cells, i.e., ATX-II inhibited both the time-dependent and the steady-state processes of Na⁺ channel inactivation. Accordingly, this toxin is a useful tool for elucidating the molecular structure of the voltage-sensitive inactivation gate of the Na⁺ channel.