Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice

SK2- and KV4.2-containing K+ channels modulate evoked synaptic potentials in CA1 pyramidal neurons. Each is coupled to a distinct Ca2+ source that provides Ca2+-dependent feedback regulation to limit AMPA receptor (AMPAR)- and NMDA receptor (NMDAR)-mediated postsynaptic depolarization. SK2-containin...

Full description

Bibliographic Details
Main Authors:	Wang, Kang, Kelley, Melissa H., Wu, Wendy W., Adelman, John P., Maylie, James
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587947/

id	pubmed-4587947
recordtype	oai_dc
spelling	pubmed-45879472015-10-02 Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice Wang, Kang Kelley, Melissa H. Wu, Wendy W. Adelman, John P. Maylie, James Research Article SK2- and KV4.2-containing K+ channels modulate evoked synaptic potentials in CA1 pyramidal neurons. Each is coupled to a distinct Ca2+ source that provides Ca2+-dependent feedback regulation to limit AMPA receptor (AMPAR)- and NMDA receptor (NMDAR)-mediated postsynaptic depolarization. SK2-containing channels are activated by Ca2+ entry through NMDARs, whereas KV4.2-containing channel availability is increased by Ca2+ entry through SNX-482 (SNX) sensitive CaV2.3 R-type Ca2+ channels. Recent studies have challenged the functional coupling between NMDARs and SK2-containing channels, suggesting that synaptic SK2-containing channels are instead activated by Ca2+ entry through R-type Ca2+ channels. Furthermore, SNX has been implicated to have off target affects, which would challenge the proposed coupling between R-type Ca2+ channels and KV4.2-containing K+ channels. To reconcile these conflicting results, we evaluated the effect of SK channel blocker apamin and R-type Ca2+ channel blocker SNX on evoked excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal neurons from CaV2.3 null mice. The results show that in the absence of CaV2.3 channels, apamin application still boosted EPSPs. The boosting effect of CaV2.3 channel blockers on EPSPs observed in neurons from wild type mice was not observed in neurons from CaV2.3 null mice. These data are consistent with a model in which SK2-containing channels are functionally coupled to NMDARs and KV4.2-containing channels to CaV2.3 channels to provide negative feedback regulation of EPSPs in the spines of CA1 pyramidal neurons. Public Library of Science 2015-09-29 /pmc/articles/PMC4587947/ /pubmed/26418566 http://dx.doi.org/10.1371/journal.pone.0139332 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Kang Kelley, Melissa H. Wu, Wendy W. Adelman, John P. Maylie, James
spellingShingle	Wang, Kang Kelley, Melissa H. Wu, Wendy W. Adelman, John P. Maylie, James Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice
author_facet	Wang, Kang Kelley, Melissa H. Wu, Wendy W. Adelman, John P. Maylie, James
author_sort	Wang, Kang
title	Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice
title_short	Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice
title_full	Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice
title_fullStr	Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice
title_full_unstemmed	Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice
title_sort	apamin boosting of synaptic potentials in cav2.3 r-type ca2+ channel null mice
description	SK2- and KV4.2-containing K+ channels modulate evoked synaptic potentials in CA1 pyramidal neurons. Each is coupled to a distinct Ca2+ source that provides Ca2+-dependent feedback regulation to limit AMPA receptor (AMPAR)- and NMDA receptor (NMDAR)-mediated postsynaptic depolarization. SK2-containing channels are activated by Ca2+ entry through NMDARs, whereas KV4.2-containing channel availability is increased by Ca2+ entry through SNX-482 (SNX) sensitive CaV2.3 R-type Ca2+ channels. Recent studies have challenged the functional coupling between NMDARs and SK2-containing channels, suggesting that synaptic SK2-containing channels are instead activated by Ca2+ entry through R-type Ca2+ channels. Furthermore, SNX has been implicated to have off target affects, which would challenge the proposed coupling between R-type Ca2+ channels and KV4.2-containing K+ channels. To reconcile these conflicting results, we evaluated the effect of SK channel blocker apamin and R-type Ca2+ channel blocker SNX on evoked excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal neurons from CaV2.3 null mice. The results show that in the absence of CaV2.3 channels, apamin application still boosted EPSPs. The boosting effect of CaV2.3 channel blockers on EPSPs observed in neurons from wild type mice was not observed in neurons from CaV2.3 null mice. These data are consistent with a model in which SK2-containing channels are functionally coupled to NMDARs and KV4.2-containing channels to CaV2.3 channels to provide negative feedback regulation of EPSPs in the spines of CA1 pyramidal neurons.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587947/
_version_	1613481661074243584

Apamin Boosting of Synaptic Potentials in CaV2.3 R-Type Ca2+ Channel Null Mice

Similar Items