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PMID: 8987780 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Role of Ca2+ ions in nicotinic facilitation of GABA release in mouse thalamus.

Léna C, Changeux JP

Abstract

Presynaptic nicotinic acetylcholine receptors (nAChRs) are present in many regions of the brain and potentially serve as targets for the pharmacological action of nicotine in vivo. To investigate their mechanism of action, we performed patch-clamp recordings in relay neurons from slices of thalamus sensory nuclei. In these nuclei, nAChR activation facilitated the release of the inhibitory neurotransmitter GABA. Micromolar concentrations of nicotinic agonists increased the frequency of miniature GABAergic synaptic currents and decreased the failure rate of evoked synaptic currents. These actions of nicotinic agonists were not observed in knock-out mice lacking the beta 2 nAChR subunit gene. Nicotinic effects were dependent on extracellular calcium ions, and they persisted when calcium was replaced by strontium or barium but not by magnesium. Furthermore, in high extracellular calcium concentrations, nicotinic agonists evoked an increase in spontaneous release lasting for minutes after removal of the agonist. This supports the view that presynaptic nAChRs facilitate the release of neurotransmitter by increasing the calcium concentrations in presynaptic nerve endings. With use of cadmium and nickel ions as selective blockers, it was found that in different sensory nuclei the presynaptic influx of calcium could result either from the activation of voltage-dependent calcium channels or from a direct influx through nAChR channels. Finally, we propose that the nicotinic facilitation of GABAergic transmission may contribute to the increase of signal-to-noise ratio observed in the thalamus in vivo during arousal.

MeSH Terms
6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology Aconitine/analogs & derivatives,pharmacology Action Potentials/drug effects Alkaloids/pharmacology Animals Arousal/physiology Atropine/pharmacology Azocines Bacterial Toxins/pharmacology Bridged Bicyclo Compounds, Heterocyclic/pharmacology Calcium/physiology Calcium Channel Blockers/pharmacology Calcium Channels/physiology Carbachol/pharmacology Cations, Divalent/pharmacology Cyanobacteria Toxins Dihydro-beta-Erythroidine/pharmacology Dimethylphenylpiperazinium Iodide/pharmacology GABA Antagonists/pharmacology Ion Transport Lobeline/pharmacology Marine Toxins/pharmacology Mice Mice, Inbred C57BL Mice, Knockout Microcystins Neurons, Afferent/physiology Nicotine/pharmacology Nicotinic Agonists/pharmacology Nicotinic Antagonists/pharmacology Patch-Clamp Techniques Potassium/pharmacology Pyridazines/pharmacology Pyridines/pharmacology Quinolizines Receptors, GABA-A/drug effects Receptors, Nicotinic/chemistry,deficiency,genetics,physiology Tetrodotoxin/pharmacology Thalamic Nuclei/metabolism gamma-Aminobutyric Acid/metabolism
Chemicals
Alkaloids Azocines Bacterial Toxins Bridged Bicyclo Compounds, Heterocyclic Calcium Channel Blockers Calcium Channels Cations, Divalent Cyanobacteria Toxins GABA Antagonists Marine Toxins Microcystins Nicotinic Agonists Nicotinic Antagonists Pyridazines Pyridines Quinolizines Receptors, GABA-A Receptors, Nicotinic methyllycaconitine Dihydro-beta-Erythroidine Tetrodotoxin cytisine Dimethylphenylpiperazinium Iodide gamma-Aminobutyric Acid Nicotine 6-Cyano-7-nitroquinoxaline-2,3-dione Atropine Carbachol gabazine Lobeline epibatidine Potassium Calcium Aconitine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Léna C
Centre National de la Recherche Scientifique Unité de Recherche Associée D1284, Institut Pasteur, Paris, France.
Changeux J P
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1997-01-15
Pages
576-85
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6573224
Subset
IM
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