Molecular Pharmacology, Vol 9, 330-335, Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics

Tetrodotoxin Inhibition of a Na⁺-Induced Conformation Change in Excitable Membranes

¹ Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada

We have observed that tetrodotoxin can inhibit a part of the sodium-dependent increase in 8-anilino-1-naphthalenesulphonate (ANS) fluorescence on guinea pig brain synaptosomes (K_i = 0.5 nM), smooth muscle plasma membrane vesicles (K_i = 100 nM), and erythtrocyte ghost membranes (K_i = 20 nM). The potassium-dependent increase of ANS fluorescence in these membrane systems (which resembles that of sodium) was not inhibited by tetrodotoxin. This inhibition by tetrodotoxin was not observed on liposomes prepared from whole lipid extracts of these membranes, or on inside-out erythrocyte ghost vesicles. Concentrations of tetrodotoxin up to 10 µM had no direct effect on ANS fluorescence. Citrate (found in all tetrodotoxin samples) had no direct effect on ANS fluorescence, or on sodium- and potassium-dependent increases in ANS fluorescence.