Current opinion in nephrology and hypertension · 2026
The role of kir4.1/Kir5.1 in mediating the effect of angiotensin-II on Na-Cl-cotransporter.
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Wang Wen-Hui, Lin Dao-Hong
Аннотация
PURPOSE OF REVIEW: Angiotensin-II plays an important role in regulating thiazide-sensitive Na-Cl-cotransporter (NCC) encoded by Slc12A3. Moreover, inwardly-rectifying-K + (Kir) channels 4.1/Kir5.1 encoded by Kcnj10 and Kcnj16 have been shown to determine NCC expression/activity. This review discusses the role of Kir4.1/Kir5.1 of distal-convoluted-tubule (DCT) in mediating the effect of angiotensin-II on NCC expression/activity.
RECENT FINDINGS: Deletion of kidney-tubule AT1aR has no significant effect on baseline-activity of Kir4.1/Kir5.1 of DCT. However, angiotensin-II acutely stimulates Kir4.1/Kir5.1-activity and hyperpolarizes basolateral membrane predominantly in the late DCT but not in early-DCT. Angiotensin-II perfusion for 24-h stimulates NCC expression/activity, this effect is absent in kidney-tubule-specific Kir4.1-knockout mice. However, angiotensin-II perfusion for 7-days is still able to increase NCC expression/activity in kidney-tubule-specific Kir4.1-knockout mice. The deletion of AT1aR completely abolishes both short-term and long-term effects of angiotensin-II on NCC. Overnight-low-salt intake stimulates Kir4.1/Kir5.1 in DCT and NCC in wild-type mice. This effect is absent in AT1aR-knockout mice and overnight-low-salt increases renal-K + -excretion in AT1aR-knockout mice.
SUMMARY: AT1aR is not required for baseline-activity of Kir4.1/Kir5.1 but it mediates the Ang-II and the effect of low-salt-intake on Kir4.1/Kir5.1. Short-term Ang-II-induced stimulation of NCC requires Kir4.1/Kir5.1. However, Ang-II also stimulates NCC by Kir4.1/Kir5.1-independent mechanism. AT1aR plays a role in maintaining K + homeostasis during low-salt-intake.
RECENT FINDINGS: Deletion of kidney-tubule AT1aR has no significant effect on baseline-activity of Kir4.1/Kir5.1 of DCT. However, angiotensin-II acutely stimulates Kir4.1/Kir5.1-activity and hyperpolarizes basolateral membrane predominantly in the late DCT but not in early-DCT. Angiotensin-II perfusion for 24-h stimulates NCC expression/activity, this effect is absent in kidney-tubule-specific Kir4.1-knockout mice. However, angiotensin-II perfusion for 7-days is still able to increase NCC expression/activity in kidney-tubule-specific Kir4.1-knockout mice. The deletion of AT1aR completely abolishes both short-term and long-term effects of angiotensin-II on NCC. Overnight-low-salt intake stimulates Kir4.1/Kir5.1 in DCT and NCC in wild-type mice. This effect is absent in AT1aR-knockout mice and overnight-low-salt increases renal-K + -excretion in AT1aR-knockout mice.
SUMMARY: AT1aR is not required for baseline-activity of Kir4.1/Kir5.1 but it mediates the Ang-II and the effect of low-salt-intake on Kir4.1/Kir5.1. Short-term Ang-II-induced stimulation of NCC requires Kir4.1/Kir5.1. However, Ang-II also stimulates NCC by Kir4.1/Kir5.1-independent mechanism. AT1aR plays a role in maintaining K + homeostasis during low-salt-intake.