Mechanosensitive ion channel Piezo2 is inhibited by D-GsMTx4

Constanza Alcaino, Kaitlyn Knutson, Philip A. Gottlieb, Gianrico Farrugia, Arthur Beyder

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)245-253
Number of pages9
JournalChannels (Austin, Tex.)
Issue number3
StatePublished - May 4 2017


  • D-GsMTx4
  • Piezo2
  • enterochromaffin cell
  • mechanosensitive ion channel
  • mechanotransduction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry


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