Minimal sodium channel pore consisting of S5-P-S6 segments preserves intracellular pharmacology

Abstract

We studied the properties of a sodium channel comprised only of S5-P-S6 region of the rat sodium channel α-subunit Nav1.4 (μ1pore). Results obtained in HEK cell lines permanently transfected with the sodium channel α-subunit or with the μ1pore were compared with data of the native HEK cells. Sodium channel blockers, tetrodotoxin and tetracaine, protect cells transfected with the complete sodium channel against death produced by incubation with veratridine. Veratridine-induced cell death in cell lines expressing the μ1pore construct is antagonised by tetracaine, but not by tetrodotoxin. Whole-cell conductance also increases in the presence of veratridine in μ1pore transfected cells and tetracaine inhibits these currents. Our pharmacological and electrophysiological data suggest that μ1pore keeps binding sites for veratridine and tetracaine, but not for TTX, and reconstitutes the permeation pathway for Na + ions.