Mechanosensitive Ion Channels as Drug Targets

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

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 nonspecialized 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.

Keywords: mechanical transduction dystrophy, glioma arrhythmia peptide

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