Referenced in: none

Automatically associated channels: Kir2.3 , Kv10.1

Title: Depth asymmetries of the pore-lining segments of the Na+ channel revealed by cysteine mutagenesis.

Authors: N Chiamvimonvat, M T Pérez-García, R Ranjan, E Marbán, G F Tomaselli

Journal, date & volume: Neuron, 1996 May , 16, 1037-47

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/8630242

Abstract
We used serial cysteine mutagenesis to study the structure of the outer vestibule and selectivity region of the voltage-gated Na channel. The voltage dependence of Cd(2+) block enabled us to determine the locations within the electrical field of cysteine-substituted mutants in the P segments of all four domains. The fractional electrical distances of the substituted cysteines were compared with the differential sensitivity to modification by sulfhydryl-specific modifying reagents. These experiments indicate that the P segment of domain II is external, while the domain IV P segment is displaced internally, compared with the first and third domain P segments. Sulfhydryls with a steep voltage dependence for Cd(2+) block produced changes in monovalent cation selectivity; these included substitutions at the presumed selectivity filter, as well as residues in the domain IV P segment not previously recognized as determinants of selectivity. A new structural model is presented in which each of the P segments contribute unique loops that penetrate the membrane to varying depths to form the channel pore.