TRPM3 is a nociceptor channel involved in the detection of noxious heat

Neuron. 2011 May 12;70(3):482-94. doi: 10.1016/j.neuron.2011.02.051.

Abstract

Transient receptor potential melastatin-3 (TRPM3) is a broadly expressed Ca(2+)-permeable nonselective cation channel. Previous work has demonstrated robust activation of TRPM3 by the neuroactive steroid pregnenolone sulfate (PS), but its in vivo gating mechanisms and functions remained poorly understood. Here, we provide evidence that TRPM3 functions as a chemo- and thermosensor in the somatosensory system. TRPM3 is molecularly and functionally expressed in a large subset of small-diameter sensory neurons from dorsal root and trigeminal ganglia, and mediates the aversive and nocifensive behavioral responses to PS. Moreover, we demonstrate that TRPM3 is steeply activated by heating and underlies heat sensitivity in a subset of sensory neurons. TRPM3-deficient mice exhibited clear deficits in their avoidance responses to noxious heat and in the development of inflammatory heat hyperalgesia. These experiments reveal an unanticipated role for TRPM3 as a thermosensitive nociceptor channel implicated in the detection of noxious heat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / therapeutic use
  • Animals
  • Behavior, Animal / drug effects
  • Blood Glucose / drug effects
  • Blood Glucose / genetics
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Capsaicin / pharmacology
  • Cell Line, Transformed
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Freund's Adjuvant / adverse effects
  • Ganglia, Spinal / cytology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / radiation effects
  • Hot Temperature / adverse effects*
  • Humans
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy
  • Hyperalgesia / genetics
  • Hyperalgesia / metabolism*
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mustard Plant
  • Nifedipine / pharmacology
  • Pain Measurement / drug effects
  • Pain Measurement / methods
  • Pain Threshold / drug effects
  • Pain Threshold / physiology*
  • Patch-Clamp Techniques
  • Plant Oils / pharmacology
  • Pregnenolone / adverse effects
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism*
  • TRPA1 Cation Channel
  • TRPM Cation Channels / antagonists & inhibitors
  • TRPM Cation Channels / deficiency
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism*
  • Telemetry / methods
  • Time Factors
  • Transfection / methods
  • Transient Receptor Potential Channels / deficiency
  • Transient Receptor Potential Channels / genetics
  • Trigeminal Ganglion / cytology

Substances

  • 3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide
  • Acrylamides
  • Blood Glucose
  • Bridged Bicyclo Compounds, Heterocyclic
  • Calcium Channel Blockers
  • Plant Oils
  • TRPA1 Cation Channel
  • TRPM Cation Channels
  • TRPM3 protein, mouse
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • pregnenolone sulfate
  • Pregnenolone
  • Freund's Adjuvant
  • Nifedipine
  • Capsaicin
  • Calcium
  • mustard oil