TWIK-Related Acid-Sensitive Potassium Channels (TASK-1) Emerge as Contributors to Tone Regulation in Renal Arteries at Alkaline pH

Shvetsova, A.A.; Lazarenko, V.S.; Gaynullina, D.K.; Tarasova, O.S.; Schubert, R.

Авторы: Shvetsova Anastasia A., Lazarenko Varvara S., Gaynullina Dina K., Tarasova Olga S., Schubert Rudolf
Журнал: Frontiers in physiology
Том: 13
Год издания: 2022
Издательство: Frontiers Research Foundation
Местоположение издательства: Switzerland
Номер статьи: 895863
DOI: 10.3389/fphys.2022.895863
Аннотация: Aim: TASK-1 channels are established regulators of pulmonary artery tone but theircontribution to the regulation of vascular tone in systemic arteries is poorly understood. Wetested the hypothesis that TASK-1 channel functional impact differs among systemicvascular beds, that this is associated with differences in their expression and may increasewith alkalization of the extracellular environment. Therefore, we evaluated the expressionlevel of TASK-1 channels and their vasomotor role in mesenteric and renal arteries.Methods: Pulmonary, mesenteric and renal arteries from male Wistar rats were used forTASK-1 channel mRNA (qPCR) and protein content (Western blotting) measurements. Thefunctional role of TASK-1 channels was studied by wire myography using the TASK-1channel blocker AVE1231. In some experiments, the endothelium was removed with a ratwhisker.Results: Expression levels of both mRNA and protein of the TASK-1 channel pore-formingsubunit were highest in pulmonary arteries, lowest in mesenteric arteries and had anintermediate value in renal arteries. Blockade of TASK-1 channels by 1 μM AVE1231increased U46619-induced contractile responses of pulmonary arteries but did not affectbasal tone and contractile responses to methoxamine of mesenteric and renal arteries atphysiological extracellular pH (pHo = 7.41). At alkaline extracellular pH = 7.75 (increase ofNaHCO3 to 52 mM) AVE1231 evoked the development of basal tone and increasedcontractile responses to low concentrations of methoxamine in renal but not mesentericarteries. This effect was independent of the endothelium.Conclusion: In the rat systemic circulation, TASK-1 channels are abundant in renalarteries and have an anticontractile function under conditions of extracellular alkalosis.
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TWIK-Related Acid-Sensitive Potassium Channels (TASK-1) Emerge as Contributors to Tone Regulation in Renal Arteries at Alkaline pHстатья

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