Differences in the properties of Na+ channels in muscle surface and T-tubular membranes revealed by tetrodotoxin derivatives

Publisher Website
Google Scholar
Abstract
The effect of ethylenediamine derivatives of tetrodotoxin (en TTXI and en TTXII) on frog skeletal muscle was studied both electrophysiologically and biochemically. Electrophysiological experiments with one of these molecules (enTTXI) showed that the concentrations needed to block the early phase of the inward sodium current (K 0.5=7 nM) are much lower than those needed to block the late phase of inward current or muscle contraction (K 0.5=40 mM). Conversely, tubular Na+ channels are more sensitive to enTTXII than are surface Na+ channels. Toxin binding to isolated muscle membranes was studied using3H-enTTXI and3H-enTTXII. The first derivative (3H-enTTXI) has a higher affinity (K d=8 nM) for Na+ channels in the surface membrane than for Na+ channels in the T-tubular membrane (K d> 20 nM). In contrast,3H-enTTXII has a higher affinity for the tubular Na+ channel (K d=0.2 nM) than for the receptor in surface membranes (K d=4 nM). We conclude that Na+ channels in muscle surface and T-tubular membranes have different toxin-binding properties, which must reflect a difference in molecular structure.