Single channel properties of mitochondrial large conductance potassium channel formed by BK-VEDEC splice variant

Abstract The activation of mitochondrial large conductance calcium-activated potassium (mitoBKCa) channels increases cell survival during ischemia/reperfusion injury of cardiac cells. The basic biophysical and pharmacological properties of mitoBKCa correspond to the properties of the BKCa channels f...

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Autores principales:	Shur Gałecka, Bogusz Kulawiak, Piotr Bednarczyk, Harpreet Singh, Adam Szewczyk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f49de50f2d0e446d8f6b5f2c3a700948
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spelling	oai:doaj.org-article:f49de50f2d0e446d8f6b5f2c3a7009482021-12-02T16:53:18ZSingle channel properties of mitochondrial large conductance potassium channel formed by BK-VEDEC splice variant10.1038/s41598-021-90465-32045-2322https://doaj.org/article/f49de50f2d0e446d8f6b5f2c3a7009482021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90465-3https://doaj.org/toc/2045-2322Abstract The activation of mitochondrial large conductance calcium-activated potassium (mitoBKCa) channels increases cell survival during ischemia/reperfusion injury of cardiac cells. The basic biophysical and pharmacological properties of mitoBKCa correspond to the properties of the BKCa channels from the plasma membrane. It has been suggested that the VEDEC splice variant of the KCNMA1 gene product encoding plasma membrane BKCa is targeted toward mitochondria. However there has been no direct evidence that this protein forms a functional channel in mitochondria. In our study, we used HEK293T cells to express the VEDEC splice variant and observed channel activity in mitochondria using the mitoplast patch-clamp technique. For the first time, we found that transient expression with the VEDEC isoform resulted in channel activity with the conductance of 290 ± 3 pS. The channel was voltage-dependent and activated by calcium ions. Moreover, the activity of the channel was stimulated by the potassium channel opener NS11021 and inhibited by hemin and paxilline, which are known BKCa channel blockers. Immunofluorescence experiments confirmed the partial colocalization of the channel within the mitochondria. From these results, we conclude that the VEDEC isoform of the BKCa channel forms a functional channel in the inner mitochondrial membrane. Additionally, our data show that HEK293T cells are a promising experimental model for expression and electrophysiological studies of mitochondrial potassium channels.Shur GałeckaBogusz KulawiakPiotr BednarczykHarpreet SinghAdam SzewczykNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shur Gałecka Bogusz Kulawiak Piotr Bednarczyk Harpreet Singh Adam Szewczyk Single channel properties of mitochondrial large conductance potassium channel formed by BK-VEDEC splice variant
description	Abstract The activation of mitochondrial large conductance calcium-activated potassium (mitoBKCa) channels increases cell survival during ischemia/reperfusion injury of cardiac cells. The basic biophysical and pharmacological properties of mitoBKCa correspond to the properties of the BKCa channels from the plasma membrane. It has been suggested that the VEDEC splice variant of the KCNMA1 gene product encoding plasma membrane BKCa is targeted toward mitochondria. However there has been no direct evidence that this protein forms a functional channel in mitochondria. In our study, we used HEK293T cells to express the VEDEC splice variant and observed channel activity in mitochondria using the mitoplast patch-clamp technique. For the first time, we found that transient expression with the VEDEC isoform resulted in channel activity with the conductance of 290 ± 3 pS. The channel was voltage-dependent and activated by calcium ions. Moreover, the activity of the channel was stimulated by the potassium channel opener NS11021 and inhibited by hemin and paxilline, which are known BKCa channel blockers. Immunofluorescence experiments confirmed the partial colocalization of the channel within the mitochondria. From these results, we conclude that the VEDEC isoform of the BKCa channel forms a functional channel in the inner mitochondrial membrane. Additionally, our data show that HEK293T cells are a promising experimental model for expression and electrophysiological studies of mitochondrial potassium channels.
format	article
author	Shur Gałecka Bogusz Kulawiak Piotr Bednarczyk Harpreet Singh Adam Szewczyk
author_facet	Shur Gałecka Bogusz Kulawiak Piotr Bednarczyk Harpreet Singh Adam Szewczyk
author_sort	Shur Gałecka
title	Single channel properties of mitochondrial large conductance potassium channel formed by BK-VEDEC splice variant
title_short	Single channel properties of mitochondrial large conductance potassium channel formed by BK-VEDEC splice variant
title_full	Single channel properties of mitochondrial large conductance potassium channel formed by BK-VEDEC splice variant
title_fullStr	Single channel properties of mitochondrial large conductance potassium channel formed by BK-VEDEC splice variant
title_full_unstemmed	Single channel properties of mitochondrial large conductance potassium channel formed by BK-VEDEC splice variant
title_sort	single channel properties of mitochondrial large conductance potassium channel formed by bk-vedec splice variant
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f49de50f2d0e446d8f6b5f2c3a700948
work_keys_str_mv	AT shurgałecka singlechannelpropertiesofmitochondriallargeconductancepotassiumchannelformedbybkvedecsplicevariant AT boguszkulawiak singlechannelpropertiesofmitochondriallargeconductancepotassiumchannelformedbybkvedecsplicevariant AT piotrbednarczyk singlechannelpropertiesofmitochondriallargeconductancepotassiumchannelformedbybkvedecsplicevariant AT harpreetsingh singlechannelpropertiesofmitochondriallargeconductancepotassiumchannelformedbybkvedecsplicevariant AT adamszewczyk singlechannelpropertiesofmitochondriallargeconductancepotassiumchannelformedbybkvedecsplicevariant
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Single channel properties of mitochondrial large conductance potassium channel formed by BK-VEDEC splice variant

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