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Cell. 2020 Mar 5;180(5):956-967.e17. doi: 10.1016/j.cell.2020.01.033. Epub 2020 Feb 20.

TACAN Is an Ion Channel Involved in Sensing Mechanical Pain.

Author information

1
Department of Physiology and Cell Information Systems, McGill University, Montreal, QC, Canada; Alan Edwards Center for Research on Pain, McGill University, Montreal, QC, Canada.
2
Department of Physics, Université de Montréal, Montreal, QC, Canada.
3
Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France.
4
Alan Edwards Center for Research on Pain, McGill University, Montreal, QC, Canada; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
5
Department of Physiology and Cell Information Systems, McGill University, Montreal, QC, Canada.
6
Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada.
7
Orthopaedic Research Laboratory, Division of Orthopaedic Surgery, McGill University, Montreal, QC, Canada; Shriners' Hospital for Children, Montreal, QC, Canada.
8
Shriners' Hospital for Children, Montreal, QC, Canada; McGill Scoliosis and Spine Research Group, McGill University, Montreal, QC, Canada.
9
Alan Edwards Center for Research on Pain, McGill University, Montreal, QC, Canada; Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada; Faculty of Dentistry, McGill University, Montreal, QC, Canada.
10
Advanced Cell Diagnostics, Newark, Toronto, ON, Canada.
11
Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
12
Department of Medicine, Firestone Institute for Respiratory Health and McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
13
Department of Physics, Université de Montréal, Montreal, QC, Canada; Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada.
14
EMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
15
Department of Physiology and Cell Information Systems, McGill University, Montreal, QC, Canada; Alan Edwards Center for Research on Pain, McGill University, Montreal, QC, Canada. Electronic address: reza.sharif@mcgill.ca.

Abstract

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Although the mechanisms for some of these functions have been identified, the molecules essential to the sense of pain have remained elusive. Here we report identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, a nociceptor-specific inducible knockout of TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli. We propose that TACAN is an ion channel that contributes to sensing mechanical pain.

KEYWORDS:

TACAN; bilayer; ion channel; mechanosensitive; mechanotransduction; nociceptor; pain; patch clamp; pillar

PMID:
32084332
DOI:
10.1016/j.cell.2020.01.033

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