THE MU-I SKELETAL-MUSCLE SODIUM-CHANNEL - MUTATION E403Q ELIMINATES SENSITIVITY TO TETRODOTOXIN BUT NOT TO MU-CONOTOXINS GIIIA AND GIIIB

Voltage-sensitive Na channels from nerve and muscle are blocked by the guanidinium toxins tetrodotoxin (TTX) and saxitoxin (STX). Mutagenesi s studies of brain RII channels have shown that glutamate 387 (E387) i s essential for current block by these toxins. We demonstrate here tha t mutation of glutamate 403 (E403) of the adult skeletal muscle mu I c hannel (corresponding to E387 of RII) also prevents current blockade b y TTX and STX, and by neo-saxitoxin. However, the mutation fails to pr event blockade by the peptide neurotoxins, mu-conotoxin GIIIA and GIII B; these toxins are thought to bind to the same or overlapping sites w ith TTX and STX. The E403Q mutation may have utility as a marker for e xogenous Na channels in transgenic expression studies, since there are no known native channels with the same pharmacological profile.