Mechanosensitive Channels: Therapeutic Targets in the Myocardium?

Ed      White

Abstract

Mechanosensitivity is a property common to many cell types. Because channels gated by mechanical stimuli (mechanosensitive channels, MSCs) are implicated in many normal and pathological cellular responses, they present a valid target for therapeutic agents. However the process of mechanotranduction, the structure, function and pharmacology of eukaryotic MSCs are not well understood and matching experimental and in vivo stimuli is difficult. With respect to the pharmacology of these channels, a further complication arises because agents that modulate the activity of MSCs may not even bind to the channel itself, but may cause their effects by changing the properties of the tension-sensing lipid bilayer and/or cytoskeleton. MSCs in the myocardium are discussed in the context of their probable role in the generation of stretch-activated arrhythmias. The actions of the three most prominent agents used to study MSCs in the heart, the lanthanide gadolinium, the aminoglycosidic antibiotic streptomycin, and a peptide toxin isolated from tarantula venom, GsMTx- 4, are compared. While all three can prevent mechanically-induced cardiac arrhythmias in experimental situations, only GsMTx-4 seems to have the potential as a novel therapeutic agent for the targeting of arrhythmias provoked by MSCs.

Keywords: Mechanosensitive channels, myocardium, gadolinium, streptomycin, GsMTx-4, cardiac arrhythmias

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