title: Functional characterization of alpha9-containing cholinergic nicotinic receptors in the rat adrenal medulla: implication in stress-induced functional plasticity.
abstract: An increase in circulating adrenal catecholamine levels constitutes one of the mechanisms whereby organisms cope with stress. Accordingly, stimulus-secretion coupling within the stressed adrenal medullary tissue undergoes persistent remodeling. In particular, cholinergic synaptic neurotransmission between splanchnic nerve terminals and chromaffin cells is upregulated in stressed rats. Since synaptic transmission is mainly supported by activation of postsynaptic neuronal acetylcholine nicotinic receptors (nAChRs), we focused our study on the role of alpha9-containing nAChRs, which have been recently described in chromaffin cells. Taking advantage of their specific blockade by the alpha-conotoxin RgIA (alpha-RgIA), we unveil novel functional roles for these receptors in the stimulus-secretion coupling of the medulla. First, we show that in rat acute adrenal slices, alpha9-containing nAChRs codistribute with synaptophysin and significantly contribute to EPSCs. Second, we show that these receptors are involved in the tonic inhibitory control exerted by cholinergic activity on gap junctional coupling between chromaffin cells, as evidenced by an increased Lucifer yellow diffusion within the medulla in alpha-RgIA-treated slices. Third, we unexpectedly found that alpha9-containing nAChRs dominantly (>70%) contribute to acetylcholine-induced current in cold-stressed rats, whereas alpha3 nAChRs are the main contributing channels in unstressed animals. Consistently, expression levels of alpha9 nAChR transcript and protein are overexpressed in cold-stressed rats. As a functional relevance, we propose that upregulation of alpha9-containing nAChR channels and ensuing dominant contribution in cholinergic signaling may be one of the mechanisms whereby adrenal medullary tissue appropriately adapts to increased splanchnic nerve electrical discharges occurring in stressful situations.
authors.affiliation: Institute of Functional Genomics, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5203, Institut National de la Santé et de la Recherche Médicale U661, University of Montpellier, 34094 Montpellier, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Colomer
authors.forename: Luis A
authors.initials: LA
authors.lastname: Olivos-Oré
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent
authors.forename: J Michael
authors.initials: JM
authors.lastname: McIntosh
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Artalejo
authors.forename: Nathalie C
authors.initials: NC
authors.lastname: Guérineau
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D003080:Cold Temperature; D004058:Diffusion; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017629:Gap Junctions / Q000502:physiology; D066298:In Vitro Techniques; D007546:Isoquinolines; D008526:Medulla Oblongata / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000109:Acetylcholine; D007546:Isoquinolines; D011978:Receptors, Nicotinic; D016708:Synaptophysin; C443079:nAChR alpha9; C017475:lucifer yellow
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