Monovalent and Divalent Cation Permeability and Block of Neuronal Nicotinic Receptor Channels in Rat Parasympathetic Ganglia

Nutter, Thomas J. and Adams, David J. (1995) Monovalent and Divalent Cation Permeability and Block of Neuronal Nicotinic Receptor Channels in Rat Parasympathetic Ganglia. Journal of General Physiology, 105 6: 701-723. doi:10.1085/jgp.105.6.701

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Author Nutter, Thomas J.
Adams, David J.
Title Monovalent and Divalent Cation Permeability and Block of Neuronal Nicotinic Receptor Channels in Rat Parasympathetic Ganglia
Journal name Journal of General Physiology   Check publisher's open access policy
ISSN 0022-1295
Publication date 1995-06
Sub-type Article (original research)
DOI 10.1085/jgp.105.6.701
Open Access Status File (Publisher version)
Volume 105
Issue 6
Start page 701
End page 723
Total pages 23
Editor Olaf S. Andersen
Place of publication Baltimore, MD
Publisher Rockefeller University Press
Language eng
Subject 320000 Medical and Health Sciences
Abstract Acetylcholine-evoked currents mediated by activation of nicotinic receptors in rat parasympathetic neurons were examined using whole-cell voltage clamp. The relative permeability of the neuronal nicotinic acetylcholine (nACh) receptor channel to monovalent and divalent inorganic and organic cations was determined from reversal potential measurements. The channel exhibited weak selectivity among the alkali metals with a selectivity sequence of Cs+ > K+ > Rb+ > Na+ > Li+, and permeability ratios relative to Na+ (Px/PNa) ranging from 1.27 to 0.75. The selectivity of the alkaline earths was also weak, with the sequence of Mg2+ > Sr2+ > Ba2+ > Ca2+, and relative permeabilities of 1.10 to 0.65. The relative Ca2+ permeability (PCa/PNa) of the neuronal nACh receptor channel is approximately fivefold higher than that of the motor endplate channel (Adams, D. J., T. M. Dwyer, and B. Hille. 1980. Journal of General Physiology. 75:493-510). The transition metal cation, Mn2+ was permeant (Px/PNa = 0.67), whereas Ni2+, Zn2+, and Cd2+ blocked ACh-evoked currents with half-maximal inhibition (IC50) occurring at approximately 500 microM, 5 microM and 1 mM, respectively. In contrast to the muscle endplate AChR channel, that at least 56 organic cations which are permeable to (Dwyer et al., 1980), the majority of organic cations tested were found to completely inhibit ACh- evoked currents in rat parasympathetic neurons. Concentration-response curves for guanidinium, ethylammonium, diethanolammonium and arginine inhibition of ACh-evoked currents yielded IC50's of approximately 2.5- 6.0 mM. The organic cations, hydrazinium, methylammonium, ethanolammonium and Tris, were measureably permeant, and permeability ratios varied inversely with the molecular size of the cation. Modeling suggests that the pore has a minimum diameter of 7.6 A. Thus, there are substantial differences in ion permeation and block between the nACh receptor channels of mammalian parasympathetic neurons and amphibian skeletal muscle which represent functional consequences of differences in the primary structure of the subunits of the ACh receptor channel.
Keyword Acetylcholine-evoked currents
nicotinic receptors
parasympathetic neurons
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Created: Fri, 07 Mar 2008, 11:21:37 EST by Thelma Whitbourne on behalf of Queensland Brain Institute