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A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel

Opening of BK-type Ca(2+) activated K(+) channels protects the heart against ischemia-reperfusion (IR) injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse per...

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Autores principales: Wojtovich, Andrew P., Nadtochiy, Sergiy M., Urciuoli, William R., Smith, Charles O., Grunnet, Morten, Nehrke, Keith, Brookes, Paul S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628382/
https://www.ncbi.nlm.nih.gov/pubmed/23638385
http://dx.doi.org/10.7717/peerj.48
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author Wojtovich, Andrew P.
Nadtochiy, Sergiy M.
Urciuoli, William R.
Smith, Charles O.
Grunnet, Morten
Nehrke, Keith
Brookes, Paul S.
author_facet Wojtovich, Andrew P.
Nadtochiy, Sergiy M.
Urciuoli, William R.
Smith, Charles O.
Grunnet, Morten
Nehrke, Keith
Brookes, Paul S.
author_sort Wojtovich, Andrew P.
collection PubMed
description Opening of BK-type Ca(2+) activated K(+) channels protects the heart against ischemia-reperfusion (IR) injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine) revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection.
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spelling pubmed-36283822013-05-01 A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel Wojtovich, Andrew P. Nadtochiy, Sergiy M. Urciuoli, William R. Smith, Charles O. Grunnet, Morten Nehrke, Keith Brookes, Paul S. Peerj Biochemistry Opening of BK-type Ca(2+) activated K(+) channels protects the heart against ischemia-reperfusion (IR) injury. However, the location of BK channels responsible for cardioprotection is debated. Herein we confirmed that openers of the SLO1 BK channel, NS1619 and NS11021, were protective in a mouse perfused heart model of IR injury. As anticipated, deletion of the Slo1 gene blocked this protection. However, in an isolated cardiomyocyte model of IR injury, protection by NS1619 and NS11021 was insensitive to Slo1 deletion. These data suggest that protection in intact hearts occurs by a non-cardiomyocyte autonomous, SLO1-dependent, mechanism. In this regard, an in-situ assay of intrinsic cardiac neuronal function (tachycardic response to nicotine) revealed that NS1619 preserved cardiac neurons following IR injury. Furthermore, blockade of synaptic transmission by hexamethonium suppressed cardioprotection by NS1619 in intact hearts. These results suggest that opening SLO1 protects the heart during IR injury, via a mechanism that involves intrinsic cardiac neurons. Cardiac neuronal ion channels may be useful therapeutic targets for eliciting cardioprotection. PeerJ Inc. 2013-03-05 /pmc/articles/PMC3628382/ /pubmed/23638385 http://dx.doi.org/10.7717/peerj.48 Text en © 2013 Wojtovich et al. http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Biochemistry
Wojtovich, Andrew P.
Nadtochiy, Sergiy M.
Urciuoli, William R.
Smith, Charles O.
Grunnet, Morten
Nehrke, Keith
Brookes, Paul S.
A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel
title A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel
title_full A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel
title_fullStr A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel
title_full_unstemmed A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel
title_short A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel
title_sort non-cardiomyocyte autonomous mechanism of cardioprotection involving the slo1 bk channel
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628382/
https://www.ncbi.nlm.nih.gov/pubmed/23638385
http://dx.doi.org/10.7717/peerj.48
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