Mechanosensitive ion channels as drug targets

Curr Drug Targets CNS Neurol Disord. 2004 Aug;3(4):287-95. doi: 10.2174/1568007043337283.

Abstract

Mechanically sensitive ion channels (MSCs) are ubiquitous. They exist as two major types: those in specialized receptors that require fibrous proteins to transmit forces to the channel, and those in non-specialized tissues that respond to stress in the lipid bilayer. While few MSCs have been cloned, the existing structures show no sequence or structural homology--an example of convergent evolution. The physiological function of MSCs in many tissues is not known, but they probably arose from the need for cell volume regulation. Recently, a peptide called GsMTx4 was isolated from tarantula venom and is the first specific reagent for mechanosensitive channels. GsMTx4 is a approximately 4 kD peptide with a hydrophobic face opposite a positively charged face. It is active in the D and L forms, and appears non-toxic to mice. GsMTx4 has shown physiological effects on cationic MSCs in heart, smooth muscle, astrocytes, and skeletal muscle. By itself, GsMTx4 can serve as a lead compound or as a potential drug. Its availability opens clinical horizons in the diagnosis and treatment of pathologies including cardiac arrhythmia, muscular dystrophy and glioma.

Publication types

  • Review

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / physiopathology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Ion Channels / drug effects*
  • Ion Channels / physiology
  • Mechanotransduction, Cellular / drug effects*
  • Mechanotransduction, Cellular / physiology
  • Muscle Cells / drug effects
  • Muscle Cells / metabolism
  • Muscular Dystrophies / drug therapy
  • Muscular Dystrophies / metabolism
  • Muscular Dystrophies / physiopathology
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Spider Venoms / pharmacology*
  • Spider Venoms / therapeutic use
  • Stress, Mechanical

Substances

  • Intercellular Signaling Peptides and Proteins
  • Ion Channels
  • MTx4 protein, Grammostola spatulata
  • Peptides
  • Spider Venoms