Role of Angiotensin II Type 1a Receptor (AT1aR) of Renal Tubules in Regulating Inwardly Rectifying Potassium Channels 4.2 (Kir4.2), Kir4.1, and Epithelial Na + Channel (ENaC).

Autor: Duan XP; Department of Physiology, Xuzhou Medical University, China (X.-P.D.).; Department of Pharmacology, New York Medical College, Valhalla (X.-P.D., Y.X., J.-Y.Z., D.-H.L., W.-H.W.)., Xiao Y; Department of Physiology, Qiqihar Medical College, Heilongjiang, China (Y.X.).; Department of Pharmacology, New York Medical College, Valhalla (X.-P.D., Y.X., J.-Y.Z., D.-H.L., W.-H.W.)., Su XT; Department of Medicine, Oregon Health & Science University, Portland (X.-T.S., S.G., J.E., C.-L.Y., J.M., D.H.E.)., Zheng JY; Department of Pharmacology, New York Medical College, Valhalla (X.-P.D., Y.X., J.-Y.Z., D.-H.L., W.-H.W.)., Gurley S; Department of Medicine, Oregon Health & Science University, Portland (X.-T.S., S.G., J.E., C.-L.Y., J.M., D.H.E.)., Emathinger J; Department of Medicine, Oregon Health & Science University, Portland (X.-T.S., S.G., J.E., C.-L.Y., J.M., D.H.E.)., Yang CL; Department of Medicine, Oregon Health & Science University, Portland (X.-T.S., S.G., J.E., C.-L.Y., J.M., D.H.E.)., McCormick J; Department of Medicine, Oregon Health & Science University, Portland (X.-T.S., S.G., J.E., C.-L.Y., J.M., D.H.E.)., Ellison DH; Department of Medicine, Oregon Health & Science University, Portland (X.-T.S., S.G., J.E., C.-L.Y., J.M., D.H.E.)., Lin DH; Department of Pharmacology, New York Medical College, Valhalla (X.-P.D., Y.X., J.-Y.Z., D.-H.L., W.-H.W.)., Wang WH; Department of Pharmacology, New York Medical College, Valhalla (X.-P.D., Y.X., J.-Y.Z., D.-H.L., W.-H.W.).
Jazyk: angličtina
Zdroj: Hypertension (Dallas, Tex. : 1979) [Hypertension] 2024 Jan; Vol. 81 (1), pp. 126-137. Date of Electronic Publication: 2023 Nov 01.
DOI: 10.1161/HYPERTENSIONAHA.123.21389
Abstrakt: Background: Kir4.2 and Kir4.1 play a role in regulating membrane transport in the proximal tubule (PT) and in the distal-convoluted-tubule (DCT), respectively.
Methods: We generated kidney-tubule-specific-AT1aR-knockout (Ks-AT1aR-KO) mice to examine whether renal AT1aR regulates Kir4.2 and Kir4.1.
Results: Ks-AT1aR-KO mice had a lower systolic blood pressure than Agtr1a flox/flox (control) mice. Ks-AT1aR-KO mice had a lower expression of NHE 3 (Na + /H + -exchanger 3) and Kir4.2, a major Kir-channel in PT, than Agtr1a flox/flox mice. Whole-cell recording also demonstrated that the membrane potential in PT of Ks-AT1aR-KO mice was lesser negative than Agtr1a flox/flox mice. The expression of Kir4.1 and Kir5.1, Kir4.1/Kir5.1-mediated K + currents of DCT and DCT membrane potential in Ks-AT1aR-KO mice, were similar to Agtr1a flox/flox mice. However, angiotensin II perfusion for 7 days hyperpolarized the membrane potential in PT and DCT of the control mice but not in Ks-AT1aR-KO mice, while angiotensin II perfusion did not change the expression of Kir4.1, Kir4.2, and Kir5.1. Deletion of AT1aR did not significantly affect the expression of αENaC (epithelial Na + channel) and βENaC but increased cleaved γENaC expression. Patch-clamp experiments demonstrated that deletion of AT1aR increased amiloride-sensitive Na + -currents in the cortical-collecting duct but not in late-DCT. However, tertiapin-Q sensitive renal outer medullary potassium channel currents were similar in both genotypes.
Conclusions: AT1aR determines the baseline membrane potential of PT by controlling Kir4.2 expression/activity but AT1aR is not required for determining the baseline membrane potential of the DCT and Kir4.1/Kir5.1 activity/expression. However, AT1aR is required for angiotensin II-induced hyperpolarization of basolateral membrane of PT and DCT. Deletion of AT1aR had no effect on baseline renal outer medullary potassium channel activity but increased ENaC activity in the CCD.
Competing Interests: Disclosures None.
Databáze: MEDLINE
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