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

Biochem Biophys Res Commun. 2005 Aug 19;334(1):140-4. doi: 10.1016/j.bbrc.2005.06.068.

Abstract

We studied the properties of a sodium channel comprised only of S5-P-S6 region of the rat sodium channel alpha-subunit Nav1.4 (micro1pore). Results obtained in HEK cell lines permanently transfected with the sodium channel alpha-subunit or with the micro1pore 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 micro1pore construct is antagonised by tetracaine, but not by tetrodotoxin. Whole-cell conductance also increases in the presence of veratridine in micro1pore transfected cells and tetracaine inhibits these currents. Our pharmacological and electrophysiological data suggest that micro1pore keeps binding sites for veratridine and tetracaine, but not for TTX, and reconstitutes the permeation pathway for Na+ ions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Cell Line
  • Humans
  • Intracellular Space / physiology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Kidney / drug effects
  • Kidney / metabolism*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Muscle Proteins / chemistry*
  • Muscle Proteins / drug effects
  • Muscle Proteins / physiology*
  • NAV1.4 Voltage-Gated Sodium Channel
  • Protein Subunits
  • Sodium Channel Blockers / pharmacology
  • Sodium Channels / chemistry*
  • Sodium Channels / drug effects
  • Sodium Channels / physiology*
  • Structure-Activity Relationship
  • Tetracaine / pharmacology
  • Tetrodotoxin / pharmacology
  • Veratridine / pharmacology

Substances

  • Muscle Proteins
  • NAV1.4 Voltage-Gated Sodium Channel
  • Protein Subunits
  • SCN4A protein, human
  • Sodium Channel Blockers
  • Sodium Channels
  • Tetracaine
  • Tetrodotoxin
  • Veratridine