Enterochromaffin () cells are the primary mechanosensors of the gastrointestinal (GI) epithelium. In response to mechanical stimuli cells release serotonin (5-hydroxytryptamine; 5-HT). The molecular details of cell mechanosensitivity are poorly understood. Recently, our group found that human and mouse cells express the mechanosensitive ion channel Piezo2. The mechanosensitive currents in a human cell model QGP-1 were blocked by the mechanosensitive channel blocker D-GsMTx4. In the present study we aimed to characterize the effects of the mechanosensitive ion channel inhibitor spider peptide D-GsMTx4 on the mechanically stimulated currents from both QGP-1 and human Piezo2 transfected HEK-293 cells. We found co-localization of 5-HT and Piezo2 in QGP-1 cells by immunohistochemistry. QGP-1 mechanosensitive currents had biophysical properties similar to dose-dependently Piezo2 and were inhibited by D-GsMTx4. In response to direct displacement of cell membranes, human Piezo2 transiently expressed in HEK-293 cells produced robust rapidly activating and inactivating inward currents. D-GsMTx4 reversibly and dose-dependently inhibited both the potency and efficacy of Piezo2 currents in response to mechanical force. Our data demonstrate an effective inhibition of Piezo2 mechanosensitive currents by the spider peptide D-GsMTx4.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463886 | PMC |
| http://dx.doi.org/10.1080/19336950.2017.1279370 | DOI Listing |
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