Functional Consequences of Chemical Modification of the Saxitoxin Binding Site on Neuronal Sodium Channels
Abstract
Voltage-dependent, saxitoxin-(STX-) sensitive sodium channels from rat brain are being studied at the single channel level in artificial planar phospholipid bilayer membranes. In the presence of the activating neurotoxin, batrachotoxin, the channels are selective for sodium over other cations, are blocked by nanomolar extracellular STX and are more likely to be open at depolarized membrane potentials. The carboxyl-specific reagent, trimethyloxonium, renders the channels insensitive to STX, reduces the rate of sodium ion permeation through the channel and greatly decreases sensitivity to block by extracellular calcium. These results have led to the development of a rate theory model of ion permeation through the sodium channels in which the STX binding site, which contains a negatively-charge carboxyl residue, is an essential step in the ion permeation process. Experimental results supporting this model place the STX binding site close enough to the mouth of the channel pore to serve as his initial binding site for permeant ions when not occupied by blockers such as calcium and STX.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 31, 1986
- Accession Number
- ADA182624
Entities
People
- Bruce K. Krueger
- Robert J. French
Organizations
- University of Maryland School of Medicine