CA SENSING RECEPTOR

EXPLORING THE FUNCTION OF EXTERNAL CALCIUM DYNAMICS IN AUDITORY HAIR CELLS

Coordinatore	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)    more  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Ms. Nome: Laurie Cognome: Louis Joseph Email: send email Telefono: 33-1-40613393 Fax: 33-1-48995407
Nazionalità Coordinatore	France [FR]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2009-RG
Funding Scheme	MC-IRG
Anno di inizio	0
Periodo (anno-mese-giorno)	0000-00-00   -   0000-00-00

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Ms. Nome: Laurie Cognome: Louis Joseph Email: send email Telefono: 33-1-40613393 Fax: 33-1-48995407	FR (PARIS)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'Hair cells of the vertebrate cochlea have the remarkable property to transduce mechanical sound waves into electrical signals at the auditory nerve fibers. This sensory activity involves tightly regulated intracellular Ca2 microdomains, both at the apical stereocilia level (Ca2 influx through the mechano-sensitive channels) and the basolateral synaptic ribbon active zones (Ca2 influx through L-type Ca2 channels). Intense hair cell activity, that is spontaneous during development or evoked by sound stimulation in mature hair cells, should produce transient focal extracellular Ca2changes ([Ca2] ext) in the endolymph and synaptic clefts. The question of [Ca2] ext signaling, while importantly addressed in central neurons, has never been investigated in auditory hair cells. Our preliminary results reveal for the first time a strong expression of the calcium sensing receptor (CaSR) in hair cells. CaSR is a G-protein-coupled membrane protein (GPCR) that detects small fluctuations in [Ca2] ext. The goal of this application is to characterize the role of CaSR in mature and developing hair cell. We will develop a method for CaSR gene silencing using in-ovo electroporation in chick embryos. We will subsequently characterize any morphological and functional changes within the inner ear. Our proposed project could provide a novel view of Ca2 homeostasis in the inner ear. This would increase our understanding of the function of Ca2 signaling in the development of auditory system and maturation of hair cells. Interestingly, in humans, mutations in the gene coding for CaSR produce deafness. Thus, this study may also contribute to the treatment of hearing disorders whose pathology lies within the developing hair cells. This project and funding will serve as part of my training towards my goal of establishing my independent research in auditory physiology.'