Down-regulation of KCa2.3 channels causes erectile dysfunction in mice

Abstract Modulation of endothelial calcium-activated K+ channels has been proposed as an approach to restore arterial endothelial cell function in disease. We hypothesized that small-conductance calcium-activated K+ channels (KCa2.3 or SK3) contributes to erectile function. The research was performe...

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Autores principales:	Simon Comerma-Steffensen, Attila Kun, Elise R. Hedegaard, Susie Mogensen, Christian Aalkjaer, Ralf Köhler, Birgitte Mønster Christensen, Ulf Simonsen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dab7db72e22f40a78a98f135e3d4f24c
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spelling	oai:doaj.org-article:dab7db72e22f40a78a98f135e3d4f24c2021-12-02T12:30:25ZDown-regulation of KCa2.3 channels causes erectile dysfunction in mice10.1038/s41598-017-04188-52045-2322https://doaj.org/article/dab7db72e22f40a78a98f135e3d4f24c2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04188-5https://doaj.org/toc/2045-2322Abstract Modulation of endothelial calcium-activated K+ channels has been proposed as an approach to restore arterial endothelial cell function in disease. We hypothesized that small-conductance calcium-activated K+ channels (KCa2.3 or SK3) contributes to erectile function. The research was performed in transgenic mice with overexpression (KCa2.3 T/T(−Dox)) or down-regulation (KCa2.3 T/T(+Dox)) of the KCa2.3 channels and wild-type C57BL/6-mice (WT). QPCR revealed that KCa2.3 and KCa1.1 channels were the most abundant in mouse corpus cavernosum. KCa2.3 channels were found by immunoreactivity and electron microscopy in the apical-lateral membrane of endothelial cells in the corpus cavernosum. Norepinephrine contraction was enhanced in the corpus cavernosum of KCa2.3 T/T(+Dox) versus KCa2.3 T/T(−Dox) mice, while acetylcholine relaxation was only reduced at 0.3 µM and relaxations in response to the nitric oxide donor sodium nitroprusside were unaltered. An opener of KCa2 channels, NS309 induced concentration-dependent relaxations of corpus cavernosum. Mean arterial pressure was lower in KCa2.3 T/T(−Dox) mice compared with WT and KCa2.3 T/T(+Dox) mice. In anesthetized mice, cavernous nerve stimulation augmented in frequency/voltage dependent manner erectile function being lower in KCa2.3 T/T(+Dox) mice at low frequencies. Our findings suggest that down-regulation of KCa2.3 channels contributes to erectile dysfunction, and that pharmacological activation of KCa2.3 channels may have the potential to restore erectile function.Simon Comerma-SteffensenAttila KunElise R. HedegaardSusie MogensenChristian AalkjaerRalf KöhlerBirgitte Mønster ChristensenUlf SimonsenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Simon Comerma-Steffensen Attila Kun Elise R. Hedegaard Susie Mogensen Christian Aalkjaer Ralf Köhler Birgitte Mønster Christensen Ulf Simonsen Down-regulation of KCa2.3 channels causes erectile dysfunction in mice
description	Abstract Modulation of endothelial calcium-activated K+ channels has been proposed as an approach to restore arterial endothelial cell function in disease. We hypothesized that small-conductance calcium-activated K+ channels (KCa2.3 or SK3) contributes to erectile function. The research was performed in transgenic mice with overexpression (KCa2.3 T/T(−Dox)) or down-regulation (KCa2.3 T/T(+Dox)) of the KCa2.3 channels and wild-type C57BL/6-mice (WT). QPCR revealed that KCa2.3 and KCa1.1 channels were the most abundant in mouse corpus cavernosum. KCa2.3 channels were found by immunoreactivity and electron microscopy in the apical-lateral membrane of endothelial cells in the corpus cavernosum. Norepinephrine contraction was enhanced in the corpus cavernosum of KCa2.3 T/T(+Dox) versus KCa2.3 T/T(−Dox) mice, while acetylcholine relaxation was only reduced at 0.3 µM and relaxations in response to the nitric oxide donor sodium nitroprusside were unaltered. An opener of KCa2 channels, NS309 induced concentration-dependent relaxations of corpus cavernosum. Mean arterial pressure was lower in KCa2.3 T/T(−Dox) mice compared with WT and KCa2.3 T/T(+Dox) mice. In anesthetized mice, cavernous nerve stimulation augmented in frequency/voltage dependent manner erectile function being lower in KCa2.3 T/T(+Dox) mice at low frequencies. Our findings suggest that down-regulation of KCa2.3 channels contributes to erectile dysfunction, and that pharmacological activation of KCa2.3 channels may have the potential to restore erectile function.
format	article
author	Simon Comerma-Steffensen Attila Kun Elise R. Hedegaard Susie Mogensen Christian Aalkjaer Ralf Köhler Birgitte Mønster Christensen Ulf Simonsen
author_facet	Simon Comerma-Steffensen Attila Kun Elise R. Hedegaard Susie Mogensen Christian Aalkjaer Ralf Köhler Birgitte Mønster Christensen Ulf Simonsen
author_sort	Simon Comerma-Steffensen
title	Down-regulation of KCa2.3 channels causes erectile dysfunction in mice
title_short	Down-regulation of KCa2.3 channels causes erectile dysfunction in mice
title_full	Down-regulation of KCa2.3 channels causes erectile dysfunction in mice
title_fullStr	Down-regulation of KCa2.3 channels causes erectile dysfunction in mice
title_full_unstemmed	Down-regulation of KCa2.3 channels causes erectile dysfunction in mice
title_sort	down-regulation of kca2.3 channels causes erectile dysfunction in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/dab7db72e22f40a78a98f135e3d4f24c
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Down-regulation of KCa2.3 channels causes erectile dysfunction in mice

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