We studied the properties of a sodium channel comprised only of S5-P-S6 region of the rat sodium channel a-subunit Nav1.4 (mu 1pore). Results obtained in HEK cell lines permanently transfected with the sodium channel a-subunit or with the mu 1pore 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 mu 1pore construct is antagonised by tetracaine, but not by tetrodotoxin. Whole-cell conductance also increases in the presence of veratridine in mu 1pore transfected cells and tetracaine inhibits these currents. Our pharmacological and electrophysiological data suggest that mu 1pore keeps binding sites for veratridine and tetracaine, but not for TTX, and reconstitutes the permeation pathway for Na+ ions. (c) 2005 Elsevier Inc. All rights reserved.