Selective modulation of neuronal nicotinic acetylcholine receptor channel subunits by G(o)-protein subunits

Fischer, H., Liu, D. M., Lee, A., Harries, J. C. and Adams, D. J. (2005) Selective modulation of neuronal nicotinic acetylcholine receptor channel subunits by G(o)-protein subunits. Journal of Neuroscience, 25 14: 3571-3577. doi:10.1523/JNEUROSCI.4971-04.2005

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Author Fischer, H.
Liu, D. M.
Lee, A.
Harries, J. C.
Adams, D. J.
Title Selective modulation of neuronal nicotinic acetylcholine receptor channel subunits by G(o)-protein subunits
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2005
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.4971-04.2005
Open Access Status File (Publisher version)
Volume 25
Issue 14
Start page 3571
End page 3577
Total pages 7
Place of publication Washington, D.C., United States
Publisher Society for Neuroscience
Collection year 2005
Language eng
Subject C1
320704 Cellular Nervous System
780105 Biological sciences
Abstract 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 GTP gamma S 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 GTP gamma S. In inside-out membrane patches, the open probability (NPo) of nAChR-mediated unitary currents was reversibly increased fourfold after bath application of 0.2mM GTP gamma S relative to control but was unchanged in the presence of GDP gamma S. 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 GTP gamma S. The direct interaction between G-protein subunits and nAChRs was examined by bath application of either G(o)alpha or G beta gamma subunits to inside-out membrane patches and in glutathione S-transferase pull-down and coimmunoprecipitation experiments. Bath application of 50 nM G beta gamma increased the open probability of ACh- activated single-channel currents fivefold, whereas G(o)alpha( 50 nM) produced no significant increase in NPo. Neuronal nAChR subunits alpha 3-alpha 5 and alpha 2 exhibited a positive interaction with G(o)alpha and G beta gamma, whereas beta 4 and alpha 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.
Keyword Cholinergic
Nicotinic Receptor
G-protein Subunits
Intracardiac Ganglia
Patch Clamp
Rat Intracardiac Ganglia
Parasympathetic Neurons
Tyrosine Kinases
Q-Index Code C1

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Created: Wed, 15 Aug 2007, 06:18:09 EST