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Impaired Kv7 channel function in cerebral arteries of a tauopathy mouse model (rTg4510)
In tauopathies, such as Alzheimer's disease with or without concomitant amyloid β plaques, cerebral arteries display pathological remodeling, leading to reduced brain tissue oxygenation and cognitive impairment. The precise mechanisms that underlie this vascular dysfunction remain unclear. Kv7...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289909/ https://www.ncbi.nlm.nih.gov/pubmed/30548427 http://dx.doi.org/10.14814/phy2.13920 |
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author | de Jong, Inge E. M. Jepps, Thomas A. |
author_facet | de Jong, Inge E. M. Jepps, Thomas A. |
author_sort | de Jong, Inge E. M. |
collection | PubMed |
description | In tauopathies, such as Alzheimer's disease with or without concomitant amyloid β plaques, cerebral arteries display pathological remodeling, leading to reduced brain tissue oxygenation and cognitive impairment. The precise mechanisms that underlie this vascular dysfunction remain unclear. Kv7 voltage‐dependent K(+) channels contribute to the development of myogenic tone in rat cerebral arteries. Thus, we hypothesized that Kv7 channel function would be impaired in the cerebral arteries of a tauopathy mouse model (rTg4510), which might underlie cerebral hypoperfusion associated with the development of neurofibrillary tangles in tauopathies. To test our hypothesis we performed wire myography and quantitative PCR on cerebral arteries, mesenteric arteries and the inferior frontotemporal region of the brain surrounding the middle cerebral artery from tau transgenic mice (rTg4510) and aged‐matched controls. We also performed whole‐cell patch clamp experiments on HEK293 cells stably expressing Kv7.4. Here, we show that Kv7 channels are functionally impaired in the cerebral arteries of rTg4510 mice, but not in mesenteric arteries from the same mice. The quantitative PCR analysis of the cerebral arteries found no change in the expression of the genes encoding the Kv7 channel α‐subunits, however, we found reduced expression of the ancillary subunit, KCNE5 (also termed KCNE1L), in the cerebral arteries of rTg4510 mice. In the brain, rTg4510 mice showed reduced expression of Kv7.3, Kv7.5, and Kv2.1. Co‐expression of KCNE5 with Kv7.4 in HEK293 cells produced larger currents at voltages >0 mV and increased the deactivation time for the Kv7.4 channel. Thus, our results demonstrate that Kv7 channel function is attenuated in the cerebral arteries of Tg4510 mice, which may result from decreased KCNE5 expression. Reduced Kv7 channel function might contribute to cerebral hypoperfusion in tauopathies, such as Alzheimer's disease. |
format | Online Article Text |
id | pubmed-6289909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62899092018-12-17 Impaired Kv7 channel function in cerebral arteries of a tauopathy mouse model (rTg4510) de Jong, Inge E. M. Jepps, Thomas A. Physiol Rep Original Research In tauopathies, such as Alzheimer's disease with or without concomitant amyloid β plaques, cerebral arteries display pathological remodeling, leading to reduced brain tissue oxygenation and cognitive impairment. The precise mechanisms that underlie this vascular dysfunction remain unclear. Kv7 voltage‐dependent K(+) channels contribute to the development of myogenic tone in rat cerebral arteries. Thus, we hypothesized that Kv7 channel function would be impaired in the cerebral arteries of a tauopathy mouse model (rTg4510), which might underlie cerebral hypoperfusion associated with the development of neurofibrillary tangles in tauopathies. To test our hypothesis we performed wire myography and quantitative PCR on cerebral arteries, mesenteric arteries and the inferior frontotemporal region of the brain surrounding the middle cerebral artery from tau transgenic mice (rTg4510) and aged‐matched controls. We also performed whole‐cell patch clamp experiments on HEK293 cells stably expressing Kv7.4. Here, we show that Kv7 channels are functionally impaired in the cerebral arteries of rTg4510 mice, but not in mesenteric arteries from the same mice. The quantitative PCR analysis of the cerebral arteries found no change in the expression of the genes encoding the Kv7 channel α‐subunits, however, we found reduced expression of the ancillary subunit, KCNE5 (also termed KCNE1L), in the cerebral arteries of rTg4510 mice. In the brain, rTg4510 mice showed reduced expression of Kv7.3, Kv7.5, and Kv2.1. Co‐expression of KCNE5 with Kv7.4 in HEK293 cells produced larger currents at voltages >0 mV and increased the deactivation time for the Kv7.4 channel. Thus, our results demonstrate that Kv7 channel function is attenuated in the cerebral arteries of Tg4510 mice, which may result from decreased KCNE5 expression. Reduced Kv7 channel function might contribute to cerebral hypoperfusion in tauopathies, such as Alzheimer's disease. John Wiley and Sons Inc. 2018-12-11 /pmc/articles/PMC6289909/ /pubmed/30548427 http://dx.doi.org/10.14814/phy2.13920 Text en © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research de Jong, Inge E. M. Jepps, Thomas A. Impaired Kv7 channel function in cerebral arteries of a tauopathy mouse model (rTg4510) |
title | Impaired Kv7 channel function in cerebral arteries of a tauopathy mouse model (rTg4510) |
title_full | Impaired Kv7 channel function in cerebral arteries of a tauopathy mouse model (rTg4510) |
title_fullStr | Impaired Kv7 channel function in cerebral arteries of a tauopathy mouse model (rTg4510) |
title_full_unstemmed | Impaired Kv7 channel function in cerebral arteries of a tauopathy mouse model (rTg4510) |
title_short | Impaired Kv7 channel function in cerebral arteries of a tauopathy mouse model (rTg4510) |
title_sort | impaired kv7 channel function in cerebral arteries of a tauopathy mouse model (rtg4510) |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289909/ https://www.ncbi.nlm.nih.gov/pubmed/30548427 http://dx.doi.org/10.14814/phy2.13920 |
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