High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain.
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, s...
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doaj-b06e7269346846589e0b2a02969871462020-11-25T02:30:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-06-0126e51510.1371/journal.pone.0000515High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain.Liam J DrewFrancois RugieroPaolo CesareJonathan E GaleBjarke AbrahamsenSarah BowdenSebastian HeinzmannMichelle RobinsonAndreas BrustBarbara CollessRichard J LewisJohn N WoodLittle 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 (IC(50) 1 microM) 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.http://europepmc.org/articles/PMC1885214?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Liam J Drew Francois Rugiero Paolo Cesare Jonathan E Gale Bjarke Abrahamsen Sarah Bowden Sebastian Heinzmann Michelle Robinson Andreas Brust Barbara Colless Richard J Lewis John N Wood |
spellingShingle |
Liam J Drew Francois Rugiero Paolo Cesare Jonathan E Gale Bjarke Abrahamsen Sarah Bowden Sebastian Heinzmann Michelle Robinson Andreas Brust Barbara Colless Richard J Lewis John N Wood High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. PLoS ONE |
author_facet |
Liam J Drew Francois Rugiero Paolo Cesare Jonathan E Gale Bjarke Abrahamsen Sarah Bowden Sebastian Heinzmann Michelle Robinson Andreas Brust Barbara Colless Richard J Lewis John N Wood |
author_sort |
Liam J Drew |
title |
High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. |
title_short |
High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. |
title_full |
High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. |
title_fullStr |
High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. |
title_full_unstemmed |
High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. |
title_sort |
high-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2007-06-01 |
description |
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 (IC(50) 1 microM) 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. |
url |
http://europepmc.org/articles/PMC1885214?pdf=render |
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