1. TRPM3 is a nociceptor channel involved in the detection of noxious heat
- Author
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Fenqin Xue, Thomas Gudermann, Julia Stab, Johannes Oberwinkler, Rudi Vennekens, Xiaodi Chen, Joris Vriens, Sara Kerselaers, Grzegorz Owsianik, Stephan E. Philipp, Bernd Nilius, Annelies Janssens, Thomas Voets, Thomas Hofmann, and Melissa Benoit
- Subjects
Blood Glucose ,Hot Temperature ,Patch-Clamp Techniques ,Time Factors ,Freund's Adjuvant ,Gating ,Membrane Potentials ,Transient receptor potential channel ,Trigeminal ganglion ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Transient Receptor Potential Channels ,Ganglia, Spinal ,Telemetry ,TRPA1 Cation Channel ,Cell Line, Transformed ,Pain Measurement ,Mice, Knockout ,0303 health sciences ,Behavior, Animal ,Chemistry ,General Neuroscience ,Anatomy ,Calcium Channel Blockers ,Trigeminal Ganglion ,Hyperalgesia ,Pregnenolone ,Nociceptor ,Pregnenolone sulfate ,Mustard Plant ,Pain Threshold ,Nifedipine ,Sensory Receptor Cells ,Neuroscience(all) ,TRPM Cation Channels ,Transfection ,03 medical and health sciences ,TRPM3 ,Animals ,Humans ,Plant Oils ,030304 developmental biology ,Inflammation ,Acrylamides ,Dose-Response Relationship, Drug ,Bridged Bicyclo Compounds, Heterocyclic ,Mice, Inbred C57BL ,Disease Models, Animal ,Gene Expression Regulation ,Calcium ,Capsaicin ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Summary 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.
- Published
- 2011