PROTEIN STRUCTURE AND FOLDING-Dependence of m-Conotoxin Block of Sodium Channels on Ionic Strength but Not on the Permeating (Na+). IMPLICATIONS FOR THE DISTINCTIVE MECHANISTIC INTERACTIONS BETWEEN

摘要: mu-Conotoxins (mu-CTXs) are Na+ channel-blocking, 22-amino acid peptides produced by the sea snail Conus geographus. Although K+ channel pore-blocking toxins show specific interactions with permeant ions and strong dependence on the ionic strength (mu), no such dependence has been reported for mu-CTX and Na+ channels. Such properties would offer insight into the binding and blocking mechanism of mu-CTX as well as functional and structural properties of the Na+ channel pore. Here we studied the effects of mu and permeant ion concentration ((Na+)) on mu-CTX block of rat skeletal muscle (mu1, Nav1.4) Na+ channels. mu-CTX sensitivity of wild-type and E758Q channels increased significantly (by apprx20-fold) when mu was lowered by substituting external Na+ with equimolar sucrose (from 140 to 35 mM Na+); however, toxin block was unaltered (p>0.05) when mu was maintained by …