Mechanosensitive ion channel Piezo2 is inhibited by D-GsMTx4. Issue 3 (4th May 2017)

• Record Type: Journal Article
• Authors: Alcaino, Constanza; Knutson, Kaitlyn; Gottlieb, Philip A.; Farrugia, Gianrico; Beyder, Arthur
• Is Part Of: Channels. Volume 11:Issue 3(2017)
• Page Start: 245
• Page End: 253
• Publication Date: 2017-05-04
• Subjects: D-GsMTx4 -- enterochromaffin cell -- mechanosensitive ion channel -- mechanotransduction -- Piezo2; Ion channels -- Periodicals; 572.3
• DOI: 10.1080/19336950.2017.1279370
• Languages: English
• ISSNs: 1933-6950

Abstract

ABSTRACT: Enterochromaffin (EC ) cells are the primary mechanosensors of the gastrointestinal (GI) epithelium. In response to mechanical stimuliEC cells release serotonin (5-hydroxytryptamine; 5-HT). The molecular details ofEC cell mechanosensitivity are poorly understood. Recently, our group found that human and mouseEC cells express the mechanosensitive ion channel Piezo2. The mechanosensitive currents in a humanEC 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.