QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 6, 2005, 25(14):3571-3577; doi:10.1523/JNEUROSCI.4971-04.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Fischer, H. Articles by Adams, D. J. Search for Related Content PubMed PubMed Citation Articles by Fischer, H. Articles by Adams, D. J.

 Previous Article  |  Next Article 

Cellular/Molecular
Selective Modulation of Neuronal Nicotinic Acetylcholine Receptor Channel Subunits by G_o-Protein Subunits

Harald Fischer, Dong-Mei Liu, Aven Lee, Janet C. Harries, and David J. Adams

School of Biomedical Sciences, University of Queensland, Brisbane, Queensland 4072, Australia

G-protein modulation of neuronal nicotinic acetylcholine receptor (nAChR) channels in rat intrinsic cardiac ganglia was examined using dialyzed whole-cell and excised membrane patch-recording configurations. Cell dialysis with GTPS increased the agonist affinity of nAChRs, resulting in a potentiation of nicotine-evoked whole-cell currents at low concentrations. ACh- and nicotine-evoked current amplitudes were increased approximately twofold in the presence of GTPS. In inside-out membrane patches, the open probability (NP_o) of nAChR-mediated unitary currents was reversibly increased fourfold after bath application of 0.2 mM GTPS relative to control but was unchanged in the presence of GDPS. The modulation of nAChR-mediated whole-cell currents was agonist specific; currents evoked by the cholinergic agonists ACh, nicotine, and 1,1-dimethyl-4-phenylpiperazinium iodide, but not cytisine or choline, were potentiated in the presence of GTPS. The direct interaction between G-protein subunits and nAChRs was examined by bath application of either G_o or G subunits to inside-out membrane patches and in glutathione S-transferase pull-down and coimmunoprecipitation experiments. Bath application of 50 nM G increased the open probability of ACh-activated single-channel currents fivefold, whereas G_o (50 nM) produced no significant increase in NP_o. Neuronal nAChR subunits 3-5 and 2 exhibited a positive interaction with G_o and G, whereas 4 and 7 failed to interact with either of the G-protein subunits. These results provide evidence for a direct interaction between nAChR and G-protein subunits, underlying the increased open probability of ACh-activated single-channel currents and potentiation of nAChR-mediated whole-cell currents in parasympathetic neurons of rat intrinsic cardiac ganglia.

Key words: cholinergic; nicotinic receptor; G-protein subunits; parasympathetic; intracardiac ganglia; patch clamp

---

Received Aug 26, 2004; revised February 21, 2005; accepted February 22, 2005.

This article has been cited by other articles:

				L. Guzman, G. Moraga-Cid, A. Avila, M. Figueroa, G. E. Yevenes, J. Fuentealba, and L. G. Aguayo Blockade of Ethanol-Induced Potentiation of Glycine Receptors by a Peptide That Interferes with G{beta}{gamma} Binding J. Pharmacol. Exp. Ther., December 1, 2009; 331(3): 933 - 939. [Abstract] [Full Text] [PDF]

				A. I. Chernyavsky, J. Arredondo, J. Qian, V. Galitovskiy, and S. A. Grando Coupling of Ionic Events to Protein Kinase Signaling Cascades upon Activation of {alpha}7 Nicotinic Receptor: COOPERATIVE REGULATION OF {alpha}2-INTEGRIN EXPRESSION AND Rho KINASE ACTIVITY J. Biol. Chem., August 14, 2009; 284(33): 22140 - 22148. [Abstract] [Full Text] [PDF]

				M. A. James, Y. Lu, Y. Liu, H. G. Vikis, and M. You RGS17, an Overexpressed Gene in Human Lung and Prostate Cancer, Induces Tumor Cell Proliferation Through the Cyclic AMP-PKA-CREB Pathway Cancer Res., March 1, 2009; 69(5): 2108 - 2116. [Abstract] [Full Text] [PDF]

				J.-x. Shen, B. Tu, and J. L. Yakel Inhibition of {alpha}7-containing nicotinic ACh receptors by muscarinic M1 ACh receptors in rat hippocampal CA1 interneurones in slices J. Physiol., March 1, 2009; 587(5): 1033 - 1042. [Abstract] [Full Text] [PDF]

				G. E. Yevenes, G. Moraga-Cid, R. W. Peoples, G. Schmalzing, and L. G. Aguayo A selective G{beta}{gamma}-linked intracellular mechanism for modulation of a ligand-gated ion channel by ethanol PNAS, December 23, 2008; 105(51): 20523 - 20528. [Abstract] [Full Text] [PDF]

				J. Arredondo, A. I. Chernyavsky, D. L. Jolkovsky, K. E. Pinkerton, and S. A. Grando Receptor-mediated tobacco toxicity: acceleration of sequential expression of {alpha}5 and {alpha}7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke FASEB J, May 1, 2008; 22(5): 1356 - 1368. [Abstract] [Full Text] [PDF]

				N. Kabbani, M. P. Woll, R. Levenson, J. M. Lindstrom, and J.-P. Changeux Intracellular complexes of the 2 subunit of the nicotinic acetylcholine receptor in brain identified by proteomics PNAS, December 18, 2007; 104(51): 20570 - 20575. [Abstract] [Full Text] [PDF]

				G. E. Yevenes, G. Moraga-Cid, L. Guzman, S. Haeger, L. Oliveira, J. Olate, G. Schmalzing, and L. G. Aguayo Molecular Determinants for G Protein beta{gamma} Modulation of Ionotropic Glycine Receptors J. Biol. Chem., December 22, 2006; 281(51): 39300 - 39307. [Abstract] [Full Text] [PDF]

				R. J. Clark, H. Fischer, S. T. Nevin, D. J. Adams, and D. J. Craik The Synthesis, Structural Characterization, and Receptor Specificity of the {alpha}-Conotoxin Vc1.1 J. Biol. Chem., August 11, 2006; 281(32): 23254 - 23263. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help