KCNQ channels show conserved ethanol block and function in ethanol behaviour.

In humans, KCNQ2/3 channels form an M-current that regulates neuronal excitability, with mutations in these channels causing benign neonatal familial convulsions. The M-current is important in mechanisms of neural plasticity underlying associative memory and in the response to ethanol, with KCNQ con...

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Autores principales:	Sonia Cavaliere, John M Gillespie, James J L Hodge
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c01fcc6412d4409ba113fd773e6ace2
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spelling	oai:doaj.org-article:0c01fcc6412d4409ba113fd773e6ace22021-11-18T08:07:07ZKCNQ channels show conserved ethanol block and function in ethanol behaviour.1932-620310.1371/journal.pone.0050279https://doaj.org/article/0c01fcc6412d4409ba113fd773e6ace22012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23209695/?tool=EBIhttps://doaj.org/toc/1932-6203In humans, KCNQ2/3 channels form an M-current that regulates neuronal excitability, with mutations in these channels causing benign neonatal familial convulsions. The M-current is important in mechanisms of neural plasticity underlying associative memory and in the response to ethanol, with KCNQ controlling the release of dopamine after ethanol exposure. We show that dKCNQ is broadly expressed in the nervous system, with targeted reduction in neuronal KCNQ increasing neural excitability and KCNQ overexpression decreasing excitability and calcium signalling, consistent with KCNQ regulating the resting membrane potential and neural release as in mammalian neurons. We show that the single KCNQ channel in Drosophila (dKCNQ) has similar electrophysiological properties to neuronal KCNQ2/3, including conserved acute sensitivity to ethanol block, with the fly channel (IC(50) = 19.8 mM) being more sensitive than its mammalian ortholog (IC(50) = 42.1 mM). This suggests that the role of KCNQ in alcohol behaviour can be determined for the first time by using Drosophila. We present evidence that loss of KCNQ function in Drosophila increased sensitivity and tolerance to the sedative effects of ethanol. Acute activation of dopaminergic neurons by heat-activated TRP channel or KCNQ-RNAi expression produced ethanol hypersensitivity, suggesting that both act via a common mechanism involving membrane depolarisation and increased dopamine signalling leading to ethanol sedation.Sonia CavaliereJohn M GillespieJames J L HodgePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e50279 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sonia Cavaliere John M Gillespie James J L Hodge KCNQ channels show conserved ethanol block and function in ethanol behaviour.
description	In humans, KCNQ2/3 channels form an M-current that regulates neuronal excitability, with mutations in these channels causing benign neonatal familial convulsions. The M-current is important in mechanisms of neural plasticity underlying associative memory and in the response to ethanol, with KCNQ controlling the release of dopamine after ethanol exposure. We show that dKCNQ is broadly expressed in the nervous system, with targeted reduction in neuronal KCNQ increasing neural excitability and KCNQ overexpression decreasing excitability and calcium signalling, consistent with KCNQ regulating the resting membrane potential and neural release as in mammalian neurons. We show that the single KCNQ channel in Drosophila (dKCNQ) has similar electrophysiological properties to neuronal KCNQ2/3, including conserved acute sensitivity to ethanol block, with the fly channel (IC(50) = 19.8 mM) being more sensitive than its mammalian ortholog (IC(50) = 42.1 mM). This suggests that the role of KCNQ in alcohol behaviour can be determined for the first time by using Drosophila. We present evidence that loss of KCNQ function in Drosophila increased sensitivity and tolerance to the sedative effects of ethanol. Acute activation of dopaminergic neurons by heat-activated TRP channel or KCNQ-RNAi expression produced ethanol hypersensitivity, suggesting that both act via a common mechanism involving membrane depolarisation and increased dopamine signalling leading to ethanol sedation.
format	article
author	Sonia Cavaliere John M Gillespie James J L Hodge
author_facet	Sonia Cavaliere John M Gillespie James J L Hodge
author_sort	Sonia Cavaliere
title	KCNQ channels show conserved ethanol block and function in ethanol behaviour.
title_short	KCNQ channels show conserved ethanol block and function in ethanol behaviour.
title_full	KCNQ channels show conserved ethanol block and function in ethanol behaviour.
title_fullStr	KCNQ channels show conserved ethanol block and function in ethanol behaviour.
title_full_unstemmed	KCNQ channels show conserved ethanol block and function in ethanol behaviour.
title_sort	kcnq channels show conserved ethanol block and function in ethanol behaviour.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0c01fcc6412d4409ba113fd773e6ace2
work_keys_str_mv	AT soniacavaliere kcnqchannelsshowconservedethanolblockandfunctioninethanolbehaviour AT johnmgillespie kcnqchannelsshowconservedethanolblockandfunctioninethanolbehaviour AT jamesjlhodge kcnqchannelsshowconservedethanolblockandfunctioninethanolbehaviour
_version_	1718422150635847680

KCNQ channels show conserved ethanol block and function in ethanol behaviour.

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