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Title

Local and global calcium signals associated with the opening of neuronal alpha7 nicotinic acetylcholine receptors
Authors
Gilbert, Dorothée
Lecchi, Marzia Maria
Arnaudeau, Serge
Bertrand, Daniel
Demaurex, Nicolas
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 effects — Animals — *Calcium Signaling/drug effects — Cell Line, Tumor — Chickens — Electrophysiological Phenomena/drug effects — Humans — Isoxazoles/pharmacology — Neurons/cytology/drug effects/*metabolism — Nicotine/pharmacology — Phenylurea Compounds/pharmacology — Receptors, Nicotinic/*metabolism — Retinal Ganglion Cells/cytology/drug effects/metabolism
Identifiers
PMID: 19038445
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Structures
Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
Research group Signaux intracellulaires (210)
Citation
(ISO format) 		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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