TY - JOUR
T1 - Heterogeneity of nicotinic receptor class and subunit mRNA expression among individual parasympathetic neurons from rat intracardiac ganglia
AU - Poth, Kevin
AU - Nutter, Thomas J.
AU - Cuevas, Javier
AU - Parker, Michael J.
AU - Adams, David J.
AU - Luetje, Charles W.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - Neurons have the potential to form thousands of distinct neuronal nicotinic receptors from the eight α and three β subunits that currently are known. In an effort to determine how much of this potential complexity is realized among individual neurons, we examined the nicotinic pharmacological and biophysical properties and receptor subunit mRNA expression patterns in individual neurons cultured from rat epicardial ganglia. Analysis of the whole-cell pharmacology of these neurons showed a diversity of responses to the agonists acetylcholine, nicotine, cytisine, and 1,1-dimethyl-4- phenylpiperazinium, suggesting that a heterogeneous population of nicotinic receptor classes, or subtypes, is expressed by individual neurons. Single- channel analysis demonstrated three distinct conductances (18, 24, and 31 pS), with patches from different neurons containing different combinations of these channel classes. We used single-cell RT-PCR to examine nicotinic acetylcholine receptor (nAChR) subunit mRNA expression by individual neurons. Although mRNAs encoding all eight neuronal nAChR subunits for which we probed (α2-α5, α7, β2-β4) were present in multicellular cultures, we found that individual epicardial neurons express distinct subsets of these nAChR subunit mRNAs. These results suggest that individual epicardial neurons express distinct arrays of nAChR subunits and that these subunits may assemble into functional receptors with distinct and variable subunit composition. This variable receptor subunit expression provides an explanation for the diversity of pharmacological and single-channel responses we have observed in individual neurons.
AB - Neurons have the potential to form thousands of distinct neuronal nicotinic receptors from the eight α and three β subunits that currently are known. In an effort to determine how much of this potential complexity is realized among individual neurons, we examined the nicotinic pharmacological and biophysical properties and receptor subunit mRNA expression patterns in individual neurons cultured from rat epicardial ganglia. Analysis of the whole-cell pharmacology of these neurons showed a diversity of responses to the agonists acetylcholine, nicotine, cytisine, and 1,1-dimethyl-4- phenylpiperazinium, suggesting that a heterogeneous population of nicotinic receptor classes, or subtypes, is expressed by individual neurons. Single- channel analysis demonstrated three distinct conductances (18, 24, and 31 pS), with patches from different neurons containing different combinations of these channel classes. We used single-cell RT-PCR to examine nicotinic acetylcholine receptor (nAChR) subunit mRNA expression by individual neurons. Although mRNAs encoding all eight neuronal nAChR subunits for which we probed (α2-α5, α7, β2-β4) were present in multicellular cultures, we found that individual epicardial neurons express distinct subsets of these nAChR subunit mRNAs. These results suggest that individual epicardial neurons express distinct arrays of nAChR subunits and that these subunits may assemble into functional receptors with distinct and variable subunit composition. This variable receptor subunit expression provides an explanation for the diversity of pharmacological and single-channel responses we have observed in individual neurons.
KW - cardiac ganglia
KW - neuronal nicotinic receptors
KW - nicotinic acetylcholine receptors
KW - nicotinic pharmacology
KW - parasympathetic ganglia
KW - single-cell RT-PCR
UR - http://www.scopus.com/inward/record.url?scp=0031021358&partnerID=8YFLogxK
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U2 - 10.1523/jneurosci.17-02-00586.1997
DO - 10.1523/jneurosci.17-02-00586.1997
M3 - Article
C2 - 8987781
AN - SCOPUS:0031021358
VL - 17
SP - 586
EP - 596
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 2
ER -