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Adenosine stimulates the basolateral 50 pS K(+) channel in renal proximal tubule via adenosine-A1 receptor

Background: The basolateral potassium channels play an important role in maintaining the membrane transport in the renal proximal tubules (PT) and adenosine receptors have been shown to regulate the trans-epithelial Na(+) absorption in the PT. The aim of the present study is to explore whether adeno...

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Autores principales: Liu, Hao, Sun, Qi, Ding, Zheng, Shi, Wensen, Wang, Wen-Hui, Zhang, Chengbiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493268/
https://www.ncbi.nlm.nih.gov/pubmed/37700760
http://dx.doi.org/10.3389/fphys.2023.1242975
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author Liu, Hao
Sun, Qi
Ding, Zheng
Shi, Wensen
Wang, Wen-Hui
Zhang, Chengbiao
author_facet Liu, Hao
Sun, Qi
Ding, Zheng
Shi, Wensen
Wang, Wen-Hui
Zhang, Chengbiao
author_sort Liu, Hao
collection PubMed
description Background: The basolateral potassium channels play an important role in maintaining the membrane transport in the renal proximal tubules (PT) and adenosine receptors have been shown to regulate the trans-epithelial Na(+) absorption in the PT. The aim of the present study is to explore whether adenosine also regulates the basolateral K(+) channel of the PT and to determine the adenosine receptor type and the signaling pathway which mediates the effect of adenosine on the K(+) channel. Methods: We have used the single channel recording to examine the basolateral K(+) channel activity in the proximal tubules of the mouse kidney. All experiments were performed in cell-attached patches. Results: Single channel recording has detected a 50 pS inwardly-rectifying K(+) channel with high channel open probability and this 50 pS K(+) channel is a predominant type K(+) channel in the basolateral membrane of the mouse PT. Adding adenosine increased 50 pS K(+) channel activity in cell-attached patches, defined by NP(o) (a product of channel Numbers and Open Probability). The adenosine-induced stimulation of the 50 pS K(+) channel was absent in the PT pretreated with DPCPX, a selective inhibitor of adenosine A1 receptor. In contrast, adenosine was still able to stimulate the 50 pS K(+) channel in the PT pretreated with CP-66713, a selective adenosine A2 receptor antagonist. This suggests that the stimulatory effect of adenosine on the 50 pS K(+) channel of the PT was mediated by adenosine-A1 receptor. Moreover, the effect of adenosine on the 50 pS K(+) channel was blocked in the PT pretreated with U-73122 or Calphostin C, suggesting that adenosine-induced stimulation of the 50 pS K(+) channels of the PT was due to the activation of phospholipase C (PLC) and protein kinase C (PKC) pathway. In contrast, the inhibition of phospholipase A2 (PLA2) with AACOCF3 or inhibition of protein kinase A (PKA) with H8 failed to block the adenosine-induced stimulation of the 50 pS K(+) channel of the PT. Conclusion: We conclude that adenosine activates the 50 pS K(+) channels in the basolateral membrane of PT via adenosine-A1 receptor. Furthermore, the effect of adenosine on the 50 pS K(+) channel is mediated by PLC-PKC signaling pathway.
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spelling pubmed-104932682023-09-12 Adenosine stimulates the basolateral 50 pS K(+) channel in renal proximal tubule via adenosine-A1 receptor Liu, Hao Sun, Qi Ding, Zheng Shi, Wensen Wang, Wen-Hui Zhang, Chengbiao Front Physiol Physiology Background: The basolateral potassium channels play an important role in maintaining the membrane transport in the renal proximal tubules (PT) and adenosine receptors have been shown to regulate the trans-epithelial Na(+) absorption in the PT. The aim of the present study is to explore whether adenosine also regulates the basolateral K(+) channel of the PT and to determine the adenosine receptor type and the signaling pathway which mediates the effect of adenosine on the K(+) channel. Methods: We have used the single channel recording to examine the basolateral K(+) channel activity in the proximal tubules of the mouse kidney. All experiments were performed in cell-attached patches. Results: Single channel recording has detected a 50 pS inwardly-rectifying K(+) channel with high channel open probability and this 50 pS K(+) channel is a predominant type K(+) channel in the basolateral membrane of the mouse PT. Adding adenosine increased 50 pS K(+) channel activity in cell-attached patches, defined by NP(o) (a product of channel Numbers and Open Probability). The adenosine-induced stimulation of the 50 pS K(+) channel was absent in the PT pretreated with DPCPX, a selective inhibitor of adenosine A1 receptor. In contrast, adenosine was still able to stimulate the 50 pS K(+) channel in the PT pretreated with CP-66713, a selective adenosine A2 receptor antagonist. This suggests that the stimulatory effect of adenosine on the 50 pS K(+) channel of the PT was mediated by adenosine-A1 receptor. Moreover, the effect of adenosine on the 50 pS K(+) channel was blocked in the PT pretreated with U-73122 or Calphostin C, suggesting that adenosine-induced stimulation of the 50 pS K(+) channels of the PT was due to the activation of phospholipase C (PLC) and protein kinase C (PKC) pathway. In contrast, the inhibition of phospholipase A2 (PLA2) with AACOCF3 or inhibition of protein kinase A (PKA) with H8 failed to block the adenosine-induced stimulation of the 50 pS K(+) channel of the PT. Conclusion: We conclude that adenosine activates the 50 pS K(+) channels in the basolateral membrane of PT via adenosine-A1 receptor. Furthermore, the effect of adenosine on the 50 pS K(+) channel is mediated by PLC-PKC signaling pathway. Frontiers Media S.A. 2023-08-28 /pmc/articles/PMC10493268/ /pubmed/37700760 http://dx.doi.org/10.3389/fphys.2023.1242975 Text en Copyright © 2023 Liu, Sun, Ding, Shi, Wang and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Liu, Hao
Sun, Qi
Ding, Zheng
Shi, Wensen
Wang, Wen-Hui
Zhang, Chengbiao
Adenosine stimulates the basolateral 50 pS K(+) channel in renal proximal tubule via adenosine-A1 receptor
title Adenosine stimulates the basolateral 50 pS K(+) channel in renal proximal tubule via adenosine-A1 receptor
title_full Adenosine stimulates the basolateral 50 pS K(+) channel in renal proximal tubule via adenosine-A1 receptor
title_fullStr Adenosine stimulates the basolateral 50 pS K(+) channel in renal proximal tubule via adenosine-A1 receptor
title_full_unstemmed Adenosine stimulates the basolateral 50 pS K(+) channel in renal proximal tubule via adenosine-A1 receptor
title_short Adenosine stimulates the basolateral 50 pS K(+) channel in renal proximal tubule via adenosine-A1 receptor
title_sort adenosine stimulates the basolateral 50 ps k(+) channel in renal proximal tubule via adenosine-a1 receptor
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10493268/
https://www.ncbi.nlm.nih.gov/pubmed/37700760
http://dx.doi.org/10.3389/fphys.2023.1242975
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