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Eur J Neurosci
2010 Mar 01;316:978-93. doi: 10.1111/j.1460-9568.2010.07133.x.
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Biochemical and functional properties of distinct nicotinic acetylcholine receptors in the superior cervical ganglion of mice with targeted deletions of nAChR subunit genes.
David R
,
Ciuraszkiewicz A
,
Simeone X
,
Orr-Urtreger A
,
Papke RL
,
McIntosh JM
,
Huck S
,
Scholze P
.
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Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in ganglia of the autonomic nervous system. Here, we determined the subunit composition of hetero-pentameric nAChRs in the mouse superior cervical ganglion (SCG), the function of distinct receptors (obtained by deletions of nAChR subunit genes) and mechanisms at the level of nAChRs that might compensate for the loss of subunits. As shown by immunoprecipitation and Western blots, wild-type (WT) mice expressed: alpha 3 beta 4 (55%), alpha 3 beta 4 alpha 5 (24%) and alpha 3 beta 4 beta 2 (21%) nAChRs. nAChRs in beta 4 knockout (KO) mice were reduced to < 15% of controls and no longer contained the alpha 5 subunit. Compound action potentials, recorded from the postganglionic (internal carotid) nerve and induced by preganglionic nerve stimulation, did not differ between alpha 5 beta 4 KO and WT mice, suggesting that the reduced number of receptors in the KO mice did not impair transganglionic transmission. Deletions of alpha 5 or beta2 did not affect the overall number of receptors and we found no evidence that the two subunits substitute for each other. In addition, dual KOs allowed us to study the functional properties of distinct alpha 3 beta4 and alpha 3 beta 2 receptors that have previously only been investigated in heterologous expression systems. The two receptors strikingly differed in the decay of macroscopic currents, the efficacy of cytisine, and their responses to the alpha-conotoxins AuIB and MII. Our data, based on biochemical and functional experiments and several mouse KO models, clarify and significantly extend previous observations on the function of nAChRs in heterologous systems and the SCG.
Albuquerque,
Mammalian nicotinic acetylcholine receptors: from structure to function.
2009, Pubmed
Albuquerque,
Mammalian nicotinic acetylcholine receptors: from structure to function.
2009,
Pubmed
Alkadhi,
Plasticity of synaptic transmission in autonomic ganglia.
2005,
Pubmed
Alkadhi,
Psychosocial stress-induced hypertension results from in vivo expression of long-term potentiation in rat sympathetic ganglia.
2005,
Pubmed
Brejc,
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors.
2001,
Pubmed
Cartier,
A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors.
1996,
Pubmed
,
Xenbase
Champtiaux,
Subunit composition of functional nicotinic receptors in dopaminergic neurons investigated with knock-out mice.
2003,
Pubmed
Champtiaux,
Knockout and knockin mice to investigate the role of nicotinic receptors in the central nervous system.
2004,
Pubmed
Chavez-Noriega,
Pharmacological characterization of recombinant human neuronal nicotinic acetylcholine receptors h alpha 2 beta 2, h alpha 2 beta 4, h alpha 3 beta 2, h alpha 3 beta 4, h alpha 4 beta 2, h alpha 4 beta 4 and h alpha 7 expressed in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Colquhoun,
Pharmacology of neuronal nicotinic acetylcholine receptor subtypes.
1997,
Pubmed
Colquhoun,
Alpha3, beta2, and beta4 form heterotrimeric neuronal nicotinic acetylcholine receptors in Xenopus oocytes.
1997,
Pubmed
,
Xenbase
Corringer,
Nicotinic receptors at the amino acid level.
2000,
Pubmed
Covernton,
Comparison of neuronal nicotinic receptors in rat sympathetic neurones with subunit pairs expressed in Xenopus oocytes.
1994,
Pubmed
,
Xenbase
Cuevas,
Two distinct classes of functional 7-containing nicotinic receptor on rat superior cervical ganglion neurons.
2000,
Pubmed
De Biasi,
Nicotinic mechanisms in the autonomic control of organ systems.
2002,
Pubmed
De Koninck,
Differential regulation of neuronal nicotinic ACh receptor subunit genes in cultured neonatal rat sympathetic neurons: specific induction of alpha 7 by membrane depolarization through a Ca2+/calmodulin-dependent kinase pathway.
1995,
Pubmed
Del Signore,
Dystrophin stabilizes alpha 3- but not alpha 7-containing nicotinic acetylcholine receptor subtypes at the postsynaptic apparatus in the mouse superior cervical ganglion.
2002,
Pubmed
Fenster,
Influence of subunit composition on desensitization of neuronal acetylcholine receptors at low concentrations of nicotine.
1997,
Pubmed
,
Xenbase
Fischer,
Selective deletion of the alpha5 subunit differentially affects somatic-dendritic versus axonally targeted nicotinic ACh receptors in mouse.
2005,
Pubmed
Gerzanich,
alpha 5 Subunit alters desensitization, pharmacology, Ca++ permeability and Ca++ modulation of human neuronal alpha 3 nicotinic receptors.
1998,
Pubmed
,
Xenbase
Gotti,
Brain nicotinic acetylcholine receptors: native subtypes and their relevance.
2006,
Pubmed
Houghtling,
Characterization of (+/-)(-)[3H]epibatidine binding to nicotinic cholinergic receptors in rat and human brain.
1995,
Pubmed
Hurst,
A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization.
2005,
Pubmed
,
Xenbase
Kedmi,
Mice lacking neuronal nicotinic acetylcholine receptor beta4-subunit and mice lacking both alpha5- and beta4-subunits are highly resistant to nicotine-induced seizures.
2004,
Pubmed
Krishnaswamy,
An activity-dependent retrograde signal induces the expression of the high-affinity choline transporter in cholinergic neurons.
2009,
Pubmed
Kristufek,
Somatic and prejunctional nicotinic receptors in cultured rat sympathetic neurones show different agonist profiles.
1999,
Pubmed
Lewis,
The ion channel properties of a rat recombinant neuronal nicotinic receptor are dependent on the host cell type.
1997,
Pubmed
,
Xenbase
Lindstrom,
Autoimmune diseases involving nicotinic receptors.
2002,
Pubmed
Luetje,
Both alpha- and beta-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylcholine receptors.
1991,
Pubmed
,
Xenbase
Luo,
alpha-conotoxin AuIB selectively blocks alpha3 beta4 nicotinic acetylcholine receptors and nicotine-evoked norepinephrine release.
1998,
Pubmed
,
Xenbase
Mandelzys,
Agonist and toxin sensitivities of ACh-evoked currents on neurons expressing multiple nicotinic ACh receptor subunits.
1995,
Pubmed
,
Xenbase
Mao,
Heterogeneity of nicotinic cholinergic receptors in rat superior cervical and nodose Ganglia.
2006,
Pubmed
McGehee,
Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons.
1995,
Pubmed
Millar,
RIC-3: a nicotinic acetylcholine receptor chaperone.
2008,
Pubmed
Moser,
Evaluating the suitability of nicotinic acetylcholine receptor antibodies for standard immunodetection procedures.
2007,
Pubmed
Nai,
Relating neuronal nicotinic acetylcholine receptor subtypes defined by subunit composition and channel function.
2003,
Pubmed
Nelson,
Functional properties of human nicotinic AChRs expressed by IMR-32 neuroblastoma cells resemble those of alpha3beta4 AChRs expressed in permanently transfected HEK cells.
2001,
Pubmed
Nelson,
Alternate stoichiometries of alpha4beta2 nicotinic acetylcholine receptors.
2003,
Pubmed
,
Xenbase
Orr-Urtreger,
Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents.
1997,
Pubmed
Papke,
Partial agonist properties of cytisine on neuronal nicotinic receptors containing the beta 2 subunit.
1994,
Pubmed
,
Xenbase
Papke,
An evaluation of neuronal nicotinic acetylcholine receptor activation by quaternary nitrogen compounds indicates that choline is selective for the alpha 7 subtype.
1996,
Pubmed
,
Xenbase
Picciotto,
Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain.
1995,
Pubmed
Pollock,
Cyclic AMP-dependent protein kinase A and protein kinase C phosphorylate alpha4beta2 nicotinic receptor subunits at distinct stages of receptor formation and maturation.
2009,
Pubmed
Putz,
Nicotinic acetylcholine receptor-subunit mRNAs in the mouse superior cervical ganglion are regulated by development but not by deletion of distinct subunit genes.
2008,
Pubmed
Rae,
Low access resistance perforated patch recordings using amphotericin B.
1991,
Pubmed
Rassadi,
A null mutation for the alpha3 nicotinic acetylcholine (ACh) receptor gene abolishes fast synaptic activity in sympathetic ganglia and reveals that ACh output from developing preganglionic terminals is regulated in an activity-dependent retrograde manner.
2005,
Pubmed
Scholze,
Catecholamine outflow from mouse and rat brain slice preparations evoked by nicotinic acetylcholine receptor activation and electrical field stimulation.
2007,
Pubmed
Severance,
The alpha7 nicotinic acetylcholine receptor subunit exists in two isoforms that contribute to functional ligand-gated ion channels.
2004,
Pubmed
,
Xenbase
Sharples,
UB-165: a novel nicotinic agonist with subtype selectivity implicates the alpha4beta2* subtype in the modulation of dopamine release from rat striatal synaptosomes.
2000,
Pubmed
,
Xenbase
Sivilotti,
Recombinant nicotinic receptors, expressed in Xenopus oocytes, do not resemble native rat sympathetic ganglion receptors in single-channel behaviour.
1997,
Pubmed
,
Xenbase
Skok,
Alpha subunit composition of nicotinic acetylcholine receptors in the rat autonomic ganglia neurons as determined with subunit-specific anti-alpha(181-192) peptide antibodies.
1999,
Pubmed
Wang,
Chronic nicotine treatment up-regulates human alpha3 beta2 but not alpha3 beta4 acetylcholine receptors stably transfected in human embryonic kidney cells.
1998,
Pubmed
,
Xenbase
Wang,
Hidden function of neuronal nicotinic acetylcholine receptor beta2 subunits in ganglionic transmission: comparison to alpha5 and beta4 subunits.
2005,
Pubmed
Wang,
Autoimmune autonomic ganglionopathy: IgG effects on ganglionic acetylcholine receptor current.
2007,
Pubmed
Wang,
Assembly of human neuronal nicotinic receptor alpha5 subunits with alpha3, beta2, and beta4 subunits.
1996,
Pubmed
,
Xenbase
Wang,
Autonomic function in mice lacking alpha5 neuronal nicotinic acetylcholine receptor subunit.
2002,
Pubmed
Wang,
The role of neuronal nicotinic acetylcholine receptor subunits in autonomic ganglia: lessons from knockout mice.
2002,
Pubmed
Wang,
Deficiency of nicotinic acetylcholine receptor beta 4 subunit causes autonomic cardiac and intestinal dysfunction.
2003,
Pubmed
Wong,
Pharmacological and physiological properties of a putative ganglionic nicotinic receptor, alpha 3 beta 4, expressed in transfected eucaryotic cells.
1995,
Pubmed
Xu,
Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor.
1999,
Pubmed
Xu,
Multiorgan autonomic dysfunction in mice lacking the beta2 and the beta4 subunits of neuronal nicotinic acetylcholine receptors.
1999,
Pubmed
Zhang,
Neuronal acetylcholine receptors that bind alpha-bungarotoxin with high affinity function as ligand-gated ion channels.
1994,
Pubmed
,
Xenbase
Zoli,
Identification of four classes of brain nicotinic receptors using beta2 mutant mice.
1998,
Pubmed
Zwart,
Four pharmacologically distinct subtypes of alpha4beta2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes.
1998,
Pubmed
,
Xenbase
