Selective tracking of FFAR3-expressing neurons supports receptor coupling to N-type calcium channels in mouse sympathetic neurons

Abstract Activation of short-chain free fatty acid receptors 3 (FFAR3) has been suggested to promote sympathetic outflow in postganglionic sympathetic neurons or hamper it by a negative coupling to N-type calcium (CaV2.2) channels. Heterogeneity of FFAR3 expression in sympathetic neurons, however, r...

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Autores principales:	Claudia Colina, Henry L. Puhl, Stephen R. Ikeda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Mouse Sympathetic Neurons Free Fatty Acid Receptor (FFAR3) Mean ICA Reporter Mice Facilitation Ratio Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9631244be06d4585a3297f63fb53db00
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spelling	oai:doaj.org-article:9631244be06d4585a3297f63fb53db002021-12-02T15:09:01ZSelective tracking of FFAR3-expressing neurons supports receptor coupling to N-type calcium channels in mouse sympathetic neurons10.1038/s41598-018-35690-z2045-2322https://doaj.org/article/9631244be06d4585a3297f63fb53db002018-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-35690-zhttps://doaj.org/toc/2045-2322Abstract Activation of short-chain free fatty acid receptors 3 (FFAR3) has been suggested to promote sympathetic outflow in postganglionic sympathetic neurons or hamper it by a negative coupling to N-type calcium (CaV2.2) channels. Heterogeneity of FFAR3 expression in sympathetic neurons, however, renders single neurons studies extremely time-consuming in wild-type mice. Previous studies demonstrated large variability of the degree of CaV2.2 channel inhibition by FFAR3 in a global population of rat sympathetic neurons. Therefore, we focused on a small subpopulation of mouse sympathetic neurons using an FFAR3 antibody and an Ffar3 reporter mouse to perform immunofluorescent and electrophysiological studies. Whole-cell patch-clamp recordings of identified FFAR3-expressing neurons from reporter mice revealed a 2.5-fold decrease in the CaV2.2-FFAR3 inhibitory coupling variability and 1.5-fold increase in the mean ICa 2+ inhibition, when compared with unlabeled neurons from wild-type mice. Further, we found that the ablation of Ffar3 gene expression in two knockout mouse models led to a complete loss-of-function. Subpopulations of sympathetic neurons are associated with discrete functional pathways. However, little is known about the neural pathways of the FFAR3-expressing subpopulation. Our data indicate that FFAR3 is expressed primarily in neurons with a vasoconstrictor phenotype. Thus, fine-tuning of chemically-coded neurotransmitters may accomplish an adequate outcome.Claudia ColinaHenry L. PuhlStephen R. IkedaNature PortfolioarticleMouse Sympathetic NeuronsFree Fatty Acid Receptor (FFAR3)Mean ICAReporter MiceFacilitation RatioMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mouse Sympathetic Neurons Free Fatty Acid Receptor (FFAR3) Mean ICA Reporter Mice Facilitation Ratio Medicine R Science Q
spellingShingle	Mouse Sympathetic Neurons Free Fatty Acid Receptor (FFAR3) Mean ICA Reporter Mice Facilitation Ratio Medicine R Science Q Claudia Colina Henry L. Puhl Stephen R. Ikeda Selective tracking of FFAR3-expressing neurons supports receptor coupling to N-type calcium channels in mouse sympathetic neurons
description	Abstract Activation of short-chain free fatty acid receptors 3 (FFAR3) has been suggested to promote sympathetic outflow in postganglionic sympathetic neurons or hamper it by a negative coupling to N-type calcium (CaV2.2) channels. Heterogeneity of FFAR3 expression in sympathetic neurons, however, renders single neurons studies extremely time-consuming in wild-type mice. Previous studies demonstrated large variability of the degree of CaV2.2 channel inhibition by FFAR3 in a global population of rat sympathetic neurons. Therefore, we focused on a small subpopulation of mouse sympathetic neurons using an FFAR3 antibody and an Ffar3 reporter mouse to perform immunofluorescent and electrophysiological studies. Whole-cell patch-clamp recordings of identified FFAR3-expressing neurons from reporter mice revealed a 2.5-fold decrease in the CaV2.2-FFAR3 inhibitory coupling variability and 1.5-fold increase in the mean ICa 2+ inhibition, when compared with unlabeled neurons from wild-type mice. Further, we found that the ablation of Ffar3 gene expression in two knockout mouse models led to a complete loss-of-function. Subpopulations of sympathetic neurons are associated with discrete functional pathways. However, little is known about the neural pathways of the FFAR3-expressing subpopulation. Our data indicate that FFAR3 is expressed primarily in neurons with a vasoconstrictor phenotype. Thus, fine-tuning of chemically-coded neurotransmitters may accomplish an adequate outcome.
format	article
author	Claudia Colina Henry L. Puhl Stephen R. Ikeda
author_facet	Claudia Colina Henry L. Puhl Stephen R. Ikeda
author_sort	Claudia Colina
title	Selective tracking of FFAR3-expressing neurons supports receptor coupling to N-type calcium channels in mouse sympathetic neurons
title_short	Selective tracking of FFAR3-expressing neurons supports receptor coupling to N-type calcium channels in mouse sympathetic neurons
title_full	Selective tracking of FFAR3-expressing neurons supports receptor coupling to N-type calcium channels in mouse sympathetic neurons
title_fullStr	Selective tracking of FFAR3-expressing neurons supports receptor coupling to N-type calcium channels in mouse sympathetic neurons
title_full_unstemmed	Selective tracking of FFAR3-expressing neurons supports receptor coupling to N-type calcium channels in mouse sympathetic neurons
title_sort	selective tracking of ffar3-expressing neurons supports receptor coupling to n-type calcium channels in mouse sympathetic neurons
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/9631244be06d4585a3297f63fb53db00
work_keys_str_mv	AT claudiacolina selectivetrackingofffar3expressingneuronssupportsreceptorcouplingtontypecalciumchannelsinmousesympatheticneurons AT henrylpuhl selectivetrackingofffar3expressingneuronssupportsreceptorcouplingtontypecalciumchannelsinmousesympatheticneurons AT stephenrikeda selectivetrackingofffar3expressingneuronssupportsreceptorcouplingtontypecalciumchannelsinmousesympatheticneurons
_version_	1718387953509597184

Selective tracking of FFAR3-expressing neurons supports receptor coupling to N-type calcium channels in mouse sympathetic neurons

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