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Curr Top Membr. 2007;59:81-109. doi: 10.1016/S1063-5823(06)59004-0. Epub 2007 Apr 17.

Properties and Mechanism of the Mechanosensitive Ion Channel Inhibitor GsMTx4, a Therapeutic Peptide Derived from Tarantula Venom.

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1
The Department of Physiology and Biophysics, Center for Single Molecule Biophysics, SUNY at Buffalo, Buffalo, New York 14214.

Abstract

Mechanosensitive ion channels (MSCs) are found in all types of cells ranging from Escherichia coli to morning glories to humans. They seem to fall into two families: those in specialized receptors, such as the hair cells of the cochlea, and those in cells not clearly differentiated for sensory duty. The physiological function of the channels in nonspecialized cells has not been demonstrated, although their activity has been demonstrated innumerable times in vitro. The only specific reagent to block MSCs isGsMTx4, a 4-kDa peptide isolated from tarantula venom. Despite being isolated from venom, it is nontoxic to mice. GsMTx4 is specific for an MSC subtype, the nonselective cation channels that may be members of the transient receptor potential (TRP) family. GsMTx4 acts as a gating modifier, increasing the energy of the open state relative to the closed state. The mirror image D enantiomer of GsMTx4 is equally active, so mode of action is not via the traditional lock and key model. GsMTx4 probably acts in the boundary lipid of the channel by changing local curvature and mechanically stressing the channel toward the closed state. Despite the lack of definitive physiological data on the function of the cationic MSCs, GsMTx4 may prove useful as a drug or lead compound that can affect physiological processes. These processes would be those driven by mechanical stress, such as blood vessel autoregulation, stress-induced contraction of smooth muscle, and Ca(2+) loading in muscular dystrophy.

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