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GIRK2 splice variants and neuronal G protein-gated K(+) channels: implications for channel function and behavior

Many neurotransmitters directly inhibit neurons by activating G protein-gated inwardly rectifying K(+) (GIRK) channels, thereby moderating the influence of excitatory input on neuronal excitability. While most neuronal GIRK channels are formed by GIRK1 and GIRK2 subunits, distinct GIRK2 isoforms gen...

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Autores principales: Marron Fernandez de Velasco, Ezequiel, Zhang, Lei, N. Vo, Baovi, Tipps, Megan, Farris, Shannon, Xia, Zhilian, Anderson, Allison, Carlblom, Nicholas, Weaver, C. David, Dudek, Serena M., Wickman, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431628/
https://www.ncbi.nlm.nih.gov/pubmed/28487514
http://dx.doi.org/10.1038/s41598-017-01820-2
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author Marron Fernandez de Velasco, Ezequiel
Zhang, Lei
N. Vo, Baovi
Tipps, Megan
Farris, Shannon
Xia, Zhilian
Anderson, Allison
Carlblom, Nicholas
Weaver, C. David
Dudek, Serena M.
Wickman, Kevin
author_facet Marron Fernandez de Velasco, Ezequiel
Zhang, Lei
N. Vo, Baovi
Tipps, Megan
Farris, Shannon
Xia, Zhilian
Anderson, Allison
Carlblom, Nicholas
Weaver, C. David
Dudek, Serena M.
Wickman, Kevin
author_sort Marron Fernandez de Velasco, Ezequiel
collection PubMed
description Many neurotransmitters directly inhibit neurons by activating G protein-gated inwardly rectifying K(+) (GIRK) channels, thereby moderating the influence of excitatory input on neuronal excitability. While most neuronal GIRK channels are formed by GIRK1 and GIRK2 subunits, distinct GIRK2 isoforms generated by alternative splicing have been identified. Here, we compared the trafficking and function of two isoforms (GIRK2a and GIRK2c) expressed individually in hippocampal pyramidal neurons lacking GIRK2. GIRK2a and GIRK2c supported comparable somato-dendritic GIRK currents in Girk2 (−/−) pyramidal neurons, although GIRK2c achieved a more uniform subcellular distribution in pyramidal neurons and supported inhibitory postsynaptic currents in distal dendrites better than GIRK2a. While over-expression of either isoform in dorsal CA1 pyramidal neurons restored contextual fear learning in a conditional Girk2 (−/−) mouse line, GIRK2a also enhanced cue fear learning. Collectively, these data indicate that GIRK2 isoform balance within a neuron can impact the processing of afferent inhibitory input and associated behavior.
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spelling pubmed-54316282017-05-16 GIRK2 splice variants and neuronal G protein-gated K(+) channels: implications for channel function and behavior Marron Fernandez de Velasco, Ezequiel Zhang, Lei N. Vo, Baovi Tipps, Megan Farris, Shannon Xia, Zhilian Anderson, Allison Carlblom, Nicholas Weaver, C. David Dudek, Serena M. Wickman, Kevin Sci Rep Article Many neurotransmitters directly inhibit neurons by activating G protein-gated inwardly rectifying K(+) (GIRK) channels, thereby moderating the influence of excitatory input on neuronal excitability. While most neuronal GIRK channels are formed by GIRK1 and GIRK2 subunits, distinct GIRK2 isoforms generated by alternative splicing have been identified. Here, we compared the trafficking and function of two isoforms (GIRK2a and GIRK2c) expressed individually in hippocampal pyramidal neurons lacking GIRK2. GIRK2a and GIRK2c supported comparable somato-dendritic GIRK currents in Girk2 (−/−) pyramidal neurons, although GIRK2c achieved a more uniform subcellular distribution in pyramidal neurons and supported inhibitory postsynaptic currents in distal dendrites better than GIRK2a. While over-expression of either isoform in dorsal CA1 pyramidal neurons restored contextual fear learning in a conditional Girk2 (−/−) mouse line, GIRK2a also enhanced cue fear learning. Collectively, these data indicate that GIRK2 isoform balance within a neuron can impact the processing of afferent inhibitory input and associated behavior. Nature Publishing Group UK 2017-05-09 /pmc/articles/PMC5431628/ /pubmed/28487514 http://dx.doi.org/10.1038/s41598-017-01820-2 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Marron Fernandez de Velasco, Ezequiel
Zhang, Lei
N. Vo, Baovi
Tipps, Megan
Farris, Shannon
Xia, Zhilian
Anderson, Allison
Carlblom, Nicholas
Weaver, C. David
Dudek, Serena M.
Wickman, Kevin
GIRK2 splice variants and neuronal G protein-gated K(+) channels: implications for channel function and behavior
title GIRK2 splice variants and neuronal G protein-gated K(+) channels: implications for channel function and behavior
title_full GIRK2 splice variants and neuronal G protein-gated K(+) channels: implications for channel function and behavior
title_fullStr GIRK2 splice variants and neuronal G protein-gated K(+) channels: implications for channel function and behavior
title_full_unstemmed GIRK2 splice variants and neuronal G protein-gated K(+) channels: implications for channel function and behavior
title_short GIRK2 splice variants and neuronal G protein-gated K(+) channels: implications for channel function and behavior
title_sort girk2 splice variants and neuronal g protein-gated k(+) channels: implications for channel function and behavior
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431628/
https://www.ncbi.nlm.nih.gov/pubmed/28487514
http://dx.doi.org/10.1038/s41598-017-01820-2
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