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Excitation of rat sympathetic neurons via M(1) muscarinic receptors independently of K(v)7 channels

The slow cholinergic transmission in autonomic ganglia is known to be mediated by an inhibition of K(v)7 channels via M(1) muscarinic acetylcholine receptors. However, in the present experiments using primary cultures of rat superior cervical ganglion neurons, the extent of depolarisation caused by...

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Autores principales: Salzer, Isabella, Gafar, Hend, Gindl, Viola, Mahlknecht, Peter, Drobny, Helmut, Boehm, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233321/
https://www.ncbi.nlm.nih.gov/pubmed/24668449
http://dx.doi.org/10.1007/s00424-014-1487-1
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author Salzer, Isabella
Gafar, Hend
Gindl, Viola
Mahlknecht, Peter
Drobny, Helmut
Boehm, Stefan
author_facet Salzer, Isabella
Gafar, Hend
Gindl, Viola
Mahlknecht, Peter
Drobny, Helmut
Boehm, Stefan
author_sort Salzer, Isabella
collection PubMed
description The slow cholinergic transmission in autonomic ganglia is known to be mediated by an inhibition of K(v)7 channels via M(1) muscarinic acetylcholine receptors. However, in the present experiments using primary cultures of rat superior cervical ganglion neurons, the extent of depolarisation caused by the M(1) receptor agonist oxotremorine M did not correlate with the extent of K(v)7 channel inhibition in the very same neuron. This observation triggered a search for additional mechanisms. As the activation of M(1) receptors leads to a boost in protein kinase C (PKC) activity in sympathetic neurons, various PKC enzymes were inhibited by different means. Interference with classical PKC isoforms led to reductions in depolarisations and in noradrenaline release elicited by oxotremorine M, but left the K(v)7 channel inhibition by the muscarinic agonist unchanged. M(1) receptor-induced depolarisations were also altered when extra- or intracellular Cl(−) concentrations were changed, as were depolarising responses to γ-aminobutyric acid. Depolarisations and noradrenaline release triggered by oxotremorine M were reduced by the non-selective Cl(−) channel blockers 4-acetamido-4′-isothiocyanato-stilbene-2,2′-disulfonic acid and niflumic acid. Oxotremorine M induced slowly rising inward currents at negative membrane potentials that were blocked by inhibitors of Ca(2+)-activated Cl(−) and TMEM16A channels and attenuated by PKC inhibitors. These channel blockers also reduced oxotremorine M-evoked noradrenaline release. Together, these results reveal that slow cholinergic excitation of sympathetic neurons involves the activation of classical PKCs and of Ca(2+)-activated Cl(−) channels in addition to the well-known inhibition of K(v)7 channels.
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spelling pubmed-42333212014-11-19 Excitation of rat sympathetic neurons via M(1) muscarinic receptors independently of K(v)7 channels Salzer, Isabella Gafar, Hend Gindl, Viola Mahlknecht, Peter Drobny, Helmut Boehm, Stefan Pflugers Arch Neuroscience The slow cholinergic transmission in autonomic ganglia is known to be mediated by an inhibition of K(v)7 channels via M(1) muscarinic acetylcholine receptors. However, in the present experiments using primary cultures of rat superior cervical ganglion neurons, the extent of depolarisation caused by the M(1) receptor agonist oxotremorine M did not correlate with the extent of K(v)7 channel inhibition in the very same neuron. This observation triggered a search for additional mechanisms. As the activation of M(1) receptors leads to a boost in protein kinase C (PKC) activity in sympathetic neurons, various PKC enzymes were inhibited by different means. Interference with classical PKC isoforms led to reductions in depolarisations and in noradrenaline release elicited by oxotremorine M, but left the K(v)7 channel inhibition by the muscarinic agonist unchanged. M(1) receptor-induced depolarisations were also altered when extra- or intracellular Cl(−) concentrations were changed, as were depolarising responses to γ-aminobutyric acid. Depolarisations and noradrenaline release triggered by oxotremorine M were reduced by the non-selective Cl(−) channel blockers 4-acetamido-4′-isothiocyanato-stilbene-2,2′-disulfonic acid and niflumic acid. Oxotremorine M induced slowly rising inward currents at negative membrane potentials that were blocked by inhibitors of Ca(2+)-activated Cl(−) and TMEM16A channels and attenuated by PKC inhibitors. These channel blockers also reduced oxotremorine M-evoked noradrenaline release. Together, these results reveal that slow cholinergic excitation of sympathetic neurons involves the activation of classical PKCs and of Ca(2+)-activated Cl(−) channels in addition to the well-known inhibition of K(v)7 channels. Springer Berlin Heidelberg 2014-03-26 2014 /pmc/articles/PMC4233321/ /pubmed/24668449 http://dx.doi.org/10.1007/s00424-014-1487-1 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Neuroscience
Salzer, Isabella
Gafar, Hend
Gindl, Viola
Mahlknecht, Peter
Drobny, Helmut
Boehm, Stefan
Excitation of rat sympathetic neurons via M(1) muscarinic receptors independently of K(v)7 channels
title Excitation of rat sympathetic neurons via M(1) muscarinic receptors independently of K(v)7 channels
title_full Excitation of rat sympathetic neurons via M(1) muscarinic receptors independently of K(v)7 channels
title_fullStr Excitation of rat sympathetic neurons via M(1) muscarinic receptors independently of K(v)7 channels
title_full_unstemmed Excitation of rat sympathetic neurons via M(1) muscarinic receptors independently of K(v)7 channels
title_short Excitation of rat sympathetic neurons via M(1) muscarinic receptors independently of K(v)7 channels
title_sort excitation of rat sympathetic neurons via m(1) muscarinic receptors independently of k(v)7 channels
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4233321/
https://www.ncbi.nlm.nih.gov/pubmed/24668449
http://dx.doi.org/10.1007/s00424-014-1487-1
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