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Local and global calcium signals associated with the opening of neuronal alpha7 nicotinic acetylcholine receptors

Published in Cell calcium. 2009, vol. 45, no. 2, p. 198-207
Abstract Neuronal nicotinic acetylcholine receptors (nAChRs) are Ca(2+)-permeable ligand-gated channels widely expressed in the central and peripheral nervous system. One of the most Ca(2+) selective isoform is the homopentameric alpha7-nAChR implicated in schizophrenia. The activity of alpha7-nAChRs is usually recorded electrophysiologically, which limits the amount of information obtained. Here, we used fluorescence imaging to record Ca(2+) transients associated with activation of the alpha7-nAChR in neuroblastoma cells stably expressing human alpha7-nAChRs. Application of nicotine (50 microM) consistently evoked transient (30s), stereotyped Ca(2+) responses that were inhibited by the selective alpha7-nAChRs antagonists methyllycaconitine (MLA) and alpha-bungarotoxin, and greatly increased and prolonged by the allosteric modulator PNU-120596 (1 microM). Unexpectedly, brief (1-5s), repetitive Ca(2+) transients of sub-micrometric dimension were observed in filopodia of cells expressing alpha7-nAChR. PNU-120596 increased the frequency and slowed the decay kinetics of these miniature Ca(2+) elevations, which were insensitive to ryanodine, preserved during hyperpolarisation, and prevented by MLA, alpha-bungarotoxin, or Ca(2+) removal. Global Ca(2+) responses were also recorded in ganglion cells of embryo chicken retina during co-application of PNU-120596 and nicotine, together with whole-cell currents and brief current bursts. These data demonstrate that Ca(2+) signals generated by alpha7-nAChRs can be recorded optically both in cell lines and in intact tissues. The possibility to image miniature Ca(2+) signals enables to map the location of functional alpha7-nAChR channel clusters within cells and to analyze their single channel properties optically. Deciphering the rich pattern of intracellular Ca(2+) signals generated by the activity of the alpha7-nAChRs will reveal the physiological role of these receptor-channels.
Keywords Allosteric Regulation/drug effectsAnimals*Calcium Signaling/drug effectsCell Line, TumorChickensElectrophysiological Phenomena/drug effectsHumansIsoxazoles/pharmacologyNeurons/cytology/drug effects/*metabolismNicotine/pharmacologyPhenylurea Compounds/pharmacologyReceptors, Nicotinic/*metabolismRetinal Ganglion Cells/cytology/drug effects/metabolism
PMID: 19038445
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Research group Signaux intracellulaires (210)
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GILBERT, Dorothée et al. Local and global calcium signals associated with the opening of neuronal alpha7 nicotinic acetylcholine receptors. In: Cell calcium, 2009, vol. 45, n° 2, p. 198-207. doi: 10.1016/j.ceca.2008.10.003 https://archive-ouverte.unige.ch/unige:19835

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Deposited on : 2012-04-23

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