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Content archived on 2022-12-23

Modulation of nicotinic acetylcholine receptor-activated channels by protein phosphorylation

Objective



The goal of this project is to study the mechanisms underlying the modulation by second messengers of nicotinic acetylcholine receptor (nAChR)-activated ionic channels in muscle, in neurons of invertebrates (snail) and in vertebrates (sympathetic ganglion of the rat).

A combination of the following techniques will be used: electrophysiology (patch-clamp, microelectrode, and intracellular dialysis recording); chemistry (synthesis of new nACh receptor-channel modulators); and fluorescence image analysis (confocal laser scanning microscopy).

The following areas will be investigated: the comparative properties of whole-cell AChR-activated currents in mouse myotubes and in sympathetic ganglia neurons; modulation of nAChR by four protein kinase systems (cAMP- and cGMP-dependent phosphorylation; the protein kinase C- and tyrosine kinase-dependent phosphorylation); the modulation of ACh-activated currents in snail neurons by cytoskeleton; the pathways involved in intracellular Ca 2+ ([Ca 2+]i) elevation at AChR-activation and the modulation of AChR channels by [Ca 2+]i.

This study will make it possible to elucidate mechanisms of nAChR channels modulation by intracellular phosphorylation and by the state of neuronal cytoskeleton.

Call for proposal

Data not available

Funding Scheme

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Coordinator

Institut National de la Santé et de la Recherche Médicale
EU contribution
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Address
Bld. de Port Royal 123
75674 Paris 14
France

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Total cost
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Participants (4)