Molecular mechanisms of neurotoxin action on voltage-gated sodium channels

Voltage-gated sodium channels are the molecular targets for a broad range o f neurotoxins that act at six or more distinct receptor sites on the channe l protein. These toxins fall into three groups. Both hydrophilic low molecu lar mass toxins and larger polypeptide toxins physically block the pore and prevent sodium conductance. Alkaloid toxins and related lipid-soluble toxi ns alter voltage-dependent gating of sodium channels via an allosteric mech anism through binding to intramembranous receptor sites. In contrast, polyp eptide toxins alter channel gating by voltage sensor trapping through bindi ng to extracellular receptor sites. The results of recent studies that defi ne the receptor sites and mechanisms of action of these diverse toxins are reviewed here. (C) 2000 Societe fracaise de biochimie et biologie moleculai re / Editions 'scientifiques et medicales Elsevier SAS.