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Abstract

Cells can respond to a variety of mechanical stimuli such as tension, pressure, and shear stress. However, the mechanisms of mechanotransduction are largely unknown. The major reason for this lies in the ambiguity of the molecular entity of cell mechanosensors. Currently only MS (mechanosensitive) channels conform to an established class of mechanosensors due to the firm and detailed analyses by electrophysiolgy. Although molecular structures of MS channels are known for limited members, higher order structures of bacterial MS channels have been resolved and their detailed structure-function studies are in progress. In contrast, molecular and biophysical analyses of eukaryote MS channels, which may attract much attention, are yet not well-studied. Although many candidate molecules have been proposed as the cell mechanosensor, currently only 2-pore-domain K channels (TREK/TRAAK) and SAKCA, a new class of MS channel introduced here, may be the subjects eligible for rigorous electrophysiological analyses. On the other hand, lack of specific blockers to MS channels is another reason why the progress in this field is slow. Gadolinium (Gd(3+)) has been extensively used as a potent blocker of MS channels, but its nonspecific actions have limited its usefulness. Very recently, a promising 35 mer peptide, which can be more specific for MS channels, named GsMTx-4 has been isolated from spider venom. This peptide is interesting because it inhibits stretch-induced atrial fibrillation, which may involve MS channel activation and thus can be used as a basis for developing a new class of drugs to cure heart failure. This short review deals with recent progresses in MS channel studies and the structure-function of SAKCA, a recently cloned MS channel from heart, as well as its interaction with the new MS channel blocker GsMTx-4.