Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival.

Neuronal calcium-activated potassium channels of the BK type are activated by membrane depolarization and intracellular Ca(2+) ions. It has been suggested that these channels may play a key neuroprotective role during and after brain ischemia, but this hypothesis has so far not been tested by select...

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Autores principales:	Yiliu Liao, Ase-Marit Kristiansen, Cecilie P Oksvold, Frode A Tuvnes, Ning Gu, Elise Rundén-Pran, Peter Ruth, Matthias Sausbier, Johan F Storm
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b73ee1a14d17429b8dcddd27a8744b41
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spelling	oai:doaj.org-article:b73ee1a14d17429b8dcddd27a8744b412021-11-18T07:00:57ZNeuronal Ca2+-activated K+ channels limit brain infarction and promote survival.1932-620310.1371/journal.pone.0015601https://doaj.org/article/b73ee1a14d17429b8dcddd27a8744b412010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21209897/?tool=EBIhttps://doaj.org/toc/1932-6203Neuronal calcium-activated potassium channels of the BK type are activated by membrane depolarization and intracellular Ca(2+) ions. It has been suggested that these channels may play a key neuroprotective role during and after brain ischemia, but this hypothesis has so far not been tested by selective BK-channel manipulations in vivo. To elucidate the in vivo contribution of neuronal BK channels in acute focal cerebral ischemia, we performed middle cerebral artery occlusion (MCAO) in mice lacking BK channels (homozygous mice lacking the BK channel alpha subunit, BK(-/-)). MCAO was performed in BK(-/-) and WT mice for 90 minutes followed by a 7-hour-reperfusion period. Coronal 1 mm thick sections were stained with 2,3,5-triphenyltetrazolium chloride to reveal the infarction area. We found that transient focal cerebral ischemia by MCAO produced larger infarct volume, more severe neurological deficits, and higher post-ischemic mortality in BK(-/-) mice compared to WT littermates. However, the regional cerebral blood flow was not significantly different between genotypes as measured by Laser Doppler (LD) flowmetry pre-ischemically, intra-ischemically, and post-ischemically, suggesting that the different impact of MCAO in BK(-/-) vs. WT was not due to vascular BK channels. Furthermore, when NMDA was injected intracerebrally in non-ischemic mice, NMDA-induced neurotoxicity was found to be larger in BK(-/-) mice compared to WT. Whole-cell patch clamp recordings from CA1 pyramidal cells in organotypic hippocampal slice cultures revealed that BK channels contribute to rapid action potential repolarization, as previously found in acute slices. When these cultures were exposed to ischemia-like conditions this induced significantly more neuronal death in BK(-/-) than in WT cultures. These results indicate that neuronal BK channels are important for protection against ischemic brain damage.Yiliu LiaoAse-Marit KristiansenCecilie P OksvoldFrode A TuvnesNing GuElise Rundén-PranPeter RuthMatthias SausbierJohan F StormPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15601 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yiliu Liao Ase-Marit Kristiansen Cecilie P Oksvold Frode A Tuvnes Ning Gu Elise Rundén-Pran Peter Ruth Matthias Sausbier Johan F Storm Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival.
description	Neuronal calcium-activated potassium channels of the BK type are activated by membrane depolarization and intracellular Ca(2+) ions. It has been suggested that these channels may play a key neuroprotective role during and after brain ischemia, but this hypothesis has so far not been tested by selective BK-channel manipulations in vivo. To elucidate the in vivo contribution of neuronal BK channels in acute focal cerebral ischemia, we performed middle cerebral artery occlusion (MCAO) in mice lacking BK channels (homozygous mice lacking the BK channel alpha subunit, BK(-/-)). MCAO was performed in BK(-/-) and WT mice for 90 minutes followed by a 7-hour-reperfusion period. Coronal 1 mm thick sections were stained with 2,3,5-triphenyltetrazolium chloride to reveal the infarction area. We found that transient focal cerebral ischemia by MCAO produced larger infarct volume, more severe neurological deficits, and higher post-ischemic mortality in BK(-/-) mice compared to WT littermates. However, the regional cerebral blood flow was not significantly different between genotypes as measured by Laser Doppler (LD) flowmetry pre-ischemically, intra-ischemically, and post-ischemically, suggesting that the different impact of MCAO in BK(-/-) vs. WT was not due to vascular BK channels. Furthermore, when NMDA was injected intracerebrally in non-ischemic mice, NMDA-induced neurotoxicity was found to be larger in BK(-/-) mice compared to WT. Whole-cell patch clamp recordings from CA1 pyramidal cells in organotypic hippocampal slice cultures revealed that BK channels contribute to rapid action potential repolarization, as previously found in acute slices. When these cultures were exposed to ischemia-like conditions this induced significantly more neuronal death in BK(-/-) than in WT cultures. These results indicate that neuronal BK channels are important for protection against ischemic brain damage.
format	article
author	Yiliu Liao Ase-Marit Kristiansen Cecilie P Oksvold Frode A Tuvnes Ning Gu Elise Rundén-Pran Peter Ruth Matthias Sausbier Johan F Storm
author_facet	Yiliu Liao Ase-Marit Kristiansen Cecilie P Oksvold Frode A Tuvnes Ning Gu Elise Rundén-Pran Peter Ruth Matthias Sausbier Johan F Storm
author_sort	Yiliu Liao
title	Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival.
title_short	Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival.
title_full	Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival.
title_fullStr	Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival.
title_full_unstemmed	Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival.
title_sort	neuronal ca2+-activated k+ channels limit brain infarction and promote survival.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/b73ee1a14d17429b8dcddd27a8744b41
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Neuronal Ca2+-activated K+ channels limit brain infarction and promote survival.

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