Barrese, V; Wehbe, Z; Linden, A; McDowell, S; Forrester, E; Povstyan, O; McCloskey, KD; Greenwood, IA
(2023)
Key role for Kv11.1 (ether-a-go-go related gene) channels in rat bladder contractility.
Physiol Rep, 11 (3).
e15583.
ISSN 2051-817X
https://doi.org/10.14814/phy2.15583
SGUL Authors: Greenwood, Iain Andrew
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Abstract
In addition, to their established role in cardiac myocytes and neurons, ion channels encoded by ether-a-go-go-related genes (ERG1-3 or kcnh2,3 and 6) (kcnh2) are functionally relevant in phasic smooth muscle. The aim of the study was to determine the expression and functional impact of ERG expression products in rat urinary bladder smooth muscle using quantitative polymerase chain reaction, immunocytochemistry, whole-cell patch-clamp and isometric tension recording. kcnh2 was expressed in rat bladder, whereas kcnh6 and kcnh3 expression were negligible. Immunofluorescence for the kcnh2 expression product Kv11.1 was detected in the membrane of isolated smooth muscle cells. Potassium currents with voltage-dependent characteristics consistent with Kv11.1 channels and sensitive to the specific blocker E4031 (1 μM) were recorded from isolated detrusor smooth muscles. Disabling Kv11.1 activity with specific blockers (E4031 and dofetilide, 0.2-20 μM) augmented spontaneous contractions to a greater extent than BKCa channel blockers, enhanced carbachol-driven activity, increased nerve stimulation-mediated contractions, and impaired β-adrenoceptor-mediated inhibitory responses. These data establish for the first time that Kv11.1 channels are key determinants of contractility in rat detrusor smooth muscle.
Item Type: | Article | ||||||
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Additional Information: | © 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | ||||||
Keywords: | BK channels, Kv11.1, detrusor smooth muscle, ether-a-go-go-related genes, kcnh2 gene, Rats, Animals, Urinary Bladder, Ether, Membrane Potentials, Muscle, Smooth, Ethyl Ethers, Ethers, Nerve Tissue Proteins, Ether-A-Go-Go Potassium Channels, Muscle, Smooth, Animals, Rats, Ethers, Ethyl Ethers, Nerve Tissue Proteins, Membrane Potentials, Ether-A-Go-Go Potassium Channels, Urinary Bladder, Ether, 0606 Physiology, 1103 Clinical Sciences, 1116 Medical Physiology | ||||||
SGUL Research Institute / Research Centre: | Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) | ||||||
Journal or Publication Title: | Physiol Rep | ||||||
ISSN: | 2051-817X | ||||||
Language: | eng | ||||||
Dates: |
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Publisher License: | Creative Commons: Attribution 4.0 | ||||||
PubMed ID: | 36750122 | ||||||
Go to PubMed abstract | |||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/115122 | ||||||
Publisher's version: | https://doi.org/10.14814/phy2.15583 |
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