High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain

Drew, Liam J., Rugiero, Francois, Cesare, Paolo, Gale, Jonathan E., Abrahamsen, Bjarke, Bowden, Sarah, Heinzmann, Sebestian, Robinson, Michelle, Brust, Andreas, Colless, Barbara, Lewis, Richard J. and Wood, John N. (2007) High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. PLoS One, 2 6: 1-11. doi:10.1371/journal.pone.0000515

Author Drew, Liam J.
Rugiero, Francois
Cesare, Paolo
Gale, Jonathan E.
Abrahamsen, Bjarke
Bowden, Sarah
Heinzmann, Sebestian
Robinson, Michelle
Brust, Andreas
Colless, Barbara
Lewis, Richard J.
Wood, John N.
Title High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2007-06-13
Sub-type Article (original research)
DOI 10.1371/journal.pone.0000515
Open Access Status DOI
Volume 2
Issue 6
Start page 1
End page 11
Total pages 11
Place of publication San Francisco, CA, U.S.A.
Publisher Public Library of Science
Collection year 2008
Language eng
Subject C1
320305 Medical Biochemistry - Proteins and Peptides
780103 Chemical sciences
Abstract Little is known about the molecular basis of somatosensory mechanotransduction in mammals. We screened a library of peptide toxins for effects on mechanically activated currents in cultured dorsal root ganglion neurons. One conopeptide analogue, termed NMB-1 for noxious mechanosensation blocker 1, selectively inhibits (IC50 1 µM) sustained mechanically activated currents in a subset of sensory neurons. Biotinylated NMB-1 retains activity and binds selectively to peripherin-positive nociceptive sensory neurons. The selectivity of NMB-1 was confirmed by the fact that it has no inhibitory effects on voltage-gated sodium and calcium channels, or ligand-gated channels such as acid-sensing ion channels or TRPA1 channels. Conversely, the tarantula toxin, GsMTx-4, which inhibits stretch-activated ion channels, had no effects on mechanically activated currents in sensory neurons. In behavioral assays, NMB-1 inhibits responses only to high intensity, painful mechanical stimulation and has no effects on low intensity mechanical stimulation or thermosensation. Unexpectedly, NMB-1 was found to also be an inhibitor of rapid FM1-43 loading (a measure of mechanotransduction) in cochlear hair cells. These data demonstrate that pharmacologically distinct channels respond to distinct types of mechanical stimuli and suggest that mechanically activated sustained currents underlie noxious mechanosensation. NMB-1 thus provides a novel diagnostic tool for the molecular definition of channels involved in hearing and pressure-evoked pain.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Fri, 11 Apr 2008, 09:30:34 EST by Cody Mudgway on behalf of Institute for Molecular Bioscience