CALCIUM CHANNEL DYNAMICS AND NOCICEPTION
Department : Neurosciences - Research axis : Biology of ion channels

Research subject

Ion channels are the main molecular substrate of cellular excitability and their dysfunction is retrieved in many neuronal pathologies including chronic pain. With a strong background on voltage gated calcium channel structure function studies, our most recent contribution to this field is 1) the identification of the role of CaV3.2 T-type calcium channels in various pain syndromes including chemotherapy induced neuropathy or irritable bowel disease [1-3], 2) the discovery of specific T-type calcium channel pharmacology [4], and 3) the engineering of methods to monitor calcium channel trafficking in vitro and in vivo.

Our aim is to focus into the pathophysiological role of these channels in pain using specific genetically engineered mice [5]. We notably monitor native T-type channel trafficking and their role in nociceptive sensory neurons in various pathologic pain syndromes. We decipher the potential therapeutic potential of different new selective T-type calcium channel ligands in pathological pain models closely related to clinical cases in a translational approach.

The skills that support our activity are the use of genetically modified mouse models and behaviour analysis of pain, intracellular calcium imaging, as well as electrophysiology. The team is included in the LABEX ICST (a French network of laboratories specialized in the study of ion channels) as well as in the French network of research on pain.

 

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Team

Team leader

Emmanuel Bourinet
DR2, CNRS


  IGF Sud 125

  04 34 35 92 48

 

Staff

Francina Agosti
Post-doctorant(e), CNRS


  IGF Sud 125

  04 34 35 92 48

 

Miriam Candelas
Doctorant(e), CNRS


  IGF Sud 125

  04 34 35 92 48

 

Guillaume Coiffard
Master 2, CNRS


  IGF Sud 105

  04 34 35 92 49

 

Maud Flacelière
IR CDD, CNRS


  IGF Sud 125

  04 34 35 92 48

 

Antoine Fruquiere
Doctorant(e), CNRS


  IGF Sud 125

  04 34 35 92 48

 

Pierre Giraud
IE CDD, CNRS


  IGF Sud 125

  04 34 35 92 48

 

Sophie Laffray
MCF, UM


  IGF Sud 125

  04 34 35 92 48

 

Pierre-Francois Mery
CR1, Inserm


  IGF Sud 125

  04 34 35 92 48

 




Major publications

  • Francois, A., N. Schuetter, S. Laffray, J. Sanguesa, A. Pizzoccaro, S. Dubel, A. Mantilleri, J. Nargeot, J. Noel, J. N. Wood, A. Moqrich, O. Pongs, and E. Bourinet. (2015). The Low-Threshold Calcium Channel Cav3.2 Determines Low-Threshold Mechanoreceptor Function, Cell Rep, 10: 370-82.
  • Reynders, A., A. Mantilleri, P. Malapert, S. Rialle, S. Nidelet, S. Laffray, C. Beurrier, E. Bourinet, and A. Moqrich. (2015). Transcriptional Profiling of Cutaneous MRGPRD Free Nerve Endings and C-LTMRs, Cell Rep, 10: 1007-19.
  • Garcia-Caballero, A., V. M. Gadotti, P. Stemkowski, N. Weiss, I. A. Souza, V. Hodgkinson, C. Bladen, L. Chen, J. Hamid, A. Pizzoccaro, M. Deage, A. Francois, E. Bourinet, and G. W. Zamponi. (2014). The Deubiquitinating Enzyme USP5 Modulates Neuropathic and Inflammatory Pain by Enhancing Cav3.2 Channel Activity, Neuron, 83: 1144-58.
  • Francois, A., N. Kerckhove, M. Meleine, A. Alloui, C. Barrere, A. Gelot, V. N. Uebele, J. J. Renger, A. Eschalier, D. Ardid, and E. Bourinet. (2013). State-dependent properties of a new T-type calcium channel blocker enhance Cav3.2 selectivity and support analgesic effects, Pain, 154: 283-93.
  • Descoeur, J., V. Pereira, A. Pizzoccaro, A. Francois, B. Ling, V. Maffre, B. Couette, J. Busserolles, C. Courteix, J. Noel, M. Lazdunski, A. Eschalier, N. Authier, and E. Bourinet. (2011). Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors, EMBO Mol Med, 3: 1-13.
 

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