Mechanosensitive ion channels as drug targets

Philip A. Gottlieb, Thomas M. Suchyna, Lyle W. Ostrow, Frederick Sachs

Research output: Contribution to journalReview article

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 ∼ 4kD 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.

Original languageEnglish (US)
Pages (from-to)287-295
Number of pages9
JournalCurrent Drug Targets: CNS and Neurological Disorders
Volume3
Issue number4
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

Keywords

  • Mechanical transduction dystrophy glioma arrhythmia peptide

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

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