Functional Consequences of Chemical Modification of the Saxitoxin Binding Site on Neuronal Sodium Channels

Sodium channels from rat brain have been studied at the single channel level in planar phospholipid bilayer membranes in the presence of the activating neurotoxins, batrachotoxin (BTX) and veratridine (VER). Three problems have been investigated. First, an Eyring rate theory model has been developed to account for ion movement through the channel under a variety of experimental conditions assuming that permeant and blocking cations interact with the toxin binding site as they enter the channel. In addition to satisfactorily describing the movement of sodium ions through the channels and block by calcium ions, the model predicted that the marginally-permeable potassium ion should be a voltage-dependent blocker. This prediction has now been verified experimentally. In order to examine the generality of voltage- dependent toxin block, we have begun to study some of the properties of veratridine (VER) activated sodium channels. Although voltage-dependent gating and voltage-dependent block by STX and TTX were similar in VER and BTX-activated channels, there appeared to be two distinct VER-activated channel types but only one BTX-activated channel. Keywords: Membranes, Ion channels, Single channels sodium, Saxitoxin, Batrachotoxin, Neurotoxins, Gonyalux, Sea anemone toxin, Veratridine, Rate theory modeling.