RT Journal Article
SR Electronic
T1 A Novel Mode of Neurotoxin Action
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 453
OP 456
VO 20
IS 3
A1 MICHIHISA MIYAKE
A1 SHOJI SHIBATA
YR 1981
UL http://molpharm.aspetjournals.org/content/20/3/453.abstract
AB 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.