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Marked oestrous cycle‐dependent regulation of rat arterial K(V)7.4 channels driven by GPER1
BACKGROUND AND PURPOSE: Kcnq‐encoded K(V)7 channels (termed K(V)7.1–5) regulate vascular smooth muscle cell (VSMC) contractility at rest and as targets of receptor‐mediated responses. However, the current data are mostly derived from males. Considering the known effects of sex, the oestrous cycle an...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091994/ https://www.ncbi.nlm.nih.gov/pubmed/36085551 http://dx.doi.org/10.1111/bph.15947 |
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author | Baldwin, Samuel N. Forrester, Elizabeth A. Homer, Natalie Z. M. Andrew, Ruth Barrese, Vincenzo Stott, Jennifer B. Isakson, Brant E. Albert, Anthony P. Greenwood, Iain A. |
author_facet | Baldwin, Samuel N. Forrester, Elizabeth A. Homer, Natalie Z. M. Andrew, Ruth Barrese, Vincenzo Stott, Jennifer B. Isakson, Brant E. Albert, Anthony P. Greenwood, Iain A. |
author_sort | Baldwin, Samuel N. |
collection | PubMed |
description | BACKGROUND AND PURPOSE: Kcnq‐encoded K(V)7 channels (termed K(V)7.1–5) regulate vascular smooth muscle cell (VSMC) contractility at rest and as targets of receptor‐mediated responses. However, the current data are mostly derived from males. Considering the known effects of sex, the oestrous cycle and sex hormones on vascular reactivity, here we have characterised the molecular and functional properties of K(V)7 channels from renal and mesenteric arteries from female Wistar rats separated into di‐oestrus and met‐oestrus (F‐D/M) and pro‐oestrus and oestrus (F‐P/E). EXPERIMENTAL APPROACH: RT‐qPCR, immunocytochemistry, proximity ligation assay and wire myography were performed in renal and mesenteric arteries. Circulating sex hormone concentrations were determined by liquid chromatography–tandem mass spectrometry. Whole‐cell electrophysiology was undertaken on cells expressing K(V)7.4 channels in association with G‐protein‐coupled oestrogen receptor 1 (GPER1). KEY RESULTS: The K(V)7.2–5 activators S‐1 and ML213 and the pan‐K(V)7 inhibitor linopirdine were more effective in arteries from F‐D/M compared with F‐P/E animals. In VSMCs isolated from F‐P/E rats, exploratory evidence indicates reduced membrane abundance of K(V)7.4 but not K(V)7.1, K(V)7.5 and Kcne4 when compared with cells from F‐D/M. Plasma oestradiol was higher in F‐P/E compared with F‐D/M, and progesterone showed the converse pattern. Oestradiol/GPER1 agonist G‐1 diminished K(V)7.4 encoded currents and ML213 relaxations and reduced the membrane abundance of K(V)7.4 and interaction between K(V)7.4 and heat shock protein 90 (HSP90), in arteries from F‐D/M but not F‐P/E. CONCLUSIONS AND IMPLICATIONS: GPER1 signalling decreased K(V)7.4 membrane abundance in conjunction with diminished interaction with HSP90, giving rise to a ‘pro‐contractile state’. |
format | Online Article Text |
id | pubmed-10091994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100919942023-04-13 Marked oestrous cycle‐dependent regulation of rat arterial K(V)7.4 channels driven by GPER1 Baldwin, Samuel N. Forrester, Elizabeth A. Homer, Natalie Z. M. Andrew, Ruth Barrese, Vincenzo Stott, Jennifer B. Isakson, Brant E. Albert, Anthony P. Greenwood, Iain A. Br J Pharmacol Research Articles BACKGROUND AND PURPOSE: Kcnq‐encoded K(V)7 channels (termed K(V)7.1–5) regulate vascular smooth muscle cell (VSMC) contractility at rest and as targets of receptor‐mediated responses. However, the current data are mostly derived from males. Considering the known effects of sex, the oestrous cycle and sex hormones on vascular reactivity, here we have characterised the molecular and functional properties of K(V)7 channels from renal and mesenteric arteries from female Wistar rats separated into di‐oestrus and met‐oestrus (F‐D/M) and pro‐oestrus and oestrus (F‐P/E). EXPERIMENTAL APPROACH: RT‐qPCR, immunocytochemistry, proximity ligation assay and wire myography were performed in renal and mesenteric arteries. Circulating sex hormone concentrations were determined by liquid chromatography–tandem mass spectrometry. Whole‐cell electrophysiology was undertaken on cells expressing K(V)7.4 channels in association with G‐protein‐coupled oestrogen receptor 1 (GPER1). KEY RESULTS: The K(V)7.2–5 activators S‐1 and ML213 and the pan‐K(V)7 inhibitor linopirdine were more effective in arteries from F‐D/M compared with F‐P/E animals. In VSMCs isolated from F‐P/E rats, exploratory evidence indicates reduced membrane abundance of K(V)7.4 but not K(V)7.1, K(V)7.5 and Kcne4 when compared with cells from F‐D/M. Plasma oestradiol was higher in F‐P/E compared with F‐D/M, and progesterone showed the converse pattern. Oestradiol/GPER1 agonist G‐1 diminished K(V)7.4 encoded currents and ML213 relaxations and reduced the membrane abundance of K(V)7.4 and interaction between K(V)7.4 and heat shock protein 90 (HSP90), in arteries from F‐D/M but not F‐P/E. CONCLUSIONS AND IMPLICATIONS: GPER1 signalling decreased K(V)7.4 membrane abundance in conjunction with diminished interaction with HSP90, giving rise to a ‘pro‐contractile state’. John Wiley and Sons Inc. 2022-10-11 2023-01 /pmc/articles/PMC10091994/ /pubmed/36085551 http://dx.doi.org/10.1111/bph.15947 Text en © 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Baldwin, Samuel N. Forrester, Elizabeth A. Homer, Natalie Z. M. Andrew, Ruth Barrese, Vincenzo Stott, Jennifer B. Isakson, Brant E. Albert, Anthony P. Greenwood, Iain A. Marked oestrous cycle‐dependent regulation of rat arterial K(V)7.4 channels driven by GPER1 |
title | Marked oestrous cycle‐dependent regulation of rat arterial K(V)7.4 channels driven by GPER1 |
title_full | Marked oestrous cycle‐dependent regulation of rat arterial K(V)7.4 channels driven by GPER1 |
title_fullStr | Marked oestrous cycle‐dependent regulation of rat arterial K(V)7.4 channels driven by GPER1 |
title_full_unstemmed | Marked oestrous cycle‐dependent regulation of rat arterial K(V)7.4 channels driven by GPER1 |
title_short | Marked oestrous cycle‐dependent regulation of rat arterial K(V)7.4 channels driven by GPER1 |
title_sort | marked oestrous cycle‐dependent regulation of rat arterial k(v)7.4 channels driven by gper1 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091994/ https://www.ncbi.nlm.nih.gov/pubmed/36085551 http://dx.doi.org/10.1111/bph.15947 |
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