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Deletion of Kir5.1 Abolished the Inhibitory Effect of High Sodium (HS) Intake on the Basolateral K Channels in the DCT and Thiazide‐Sensitive Na‐Cl Cotransport (NCC)
Author(s) -
Lin Daohong,
Wu Peng,
Zhang Dandan,
Gao Zhong-Xiuzi,
Duan Xinpeng,
Xiao Yu
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02040
Subject(s) - distal convoluted tubule , chemistry , sodium , cotransporter , endocrinology , epithelial polarity , symporter , medicine , transporter , membrane , reabsorption , biochemistry , gene , organic chemistry
Background We have previously demonstrated that dietary sodium intake regulated the basolateral Kir4.1/Kir5.1 channel activity in the distal convoluted tubule (DCT) such that low sodium (LS) intake stimulated whereas HS intake inhibited the Kir4.1/Kir5.1 in the DCT. The HS‐induced inhibition of basolateral Kir4.1/Kir5.1 in the DCT was essential for the HS‐induced inhibition of NCC because HS failed to inhibit NCC in the kidney‐specific Kir4.1 knockout mice. While Kir4.1 is responsible for permeating the basolateral K conductance, Kir5.1 is an important regulatory subunit of the basolateral K channel of the DCT. The aim of the present study is to explore the role of Kir5.1 in mediating the effect of HS on the basolateral K conductance of the DCT and NCC expression/activity. Methods We have used the whole‐cell recording technique to measure the basolateral K (Kir4.1) conductance and DCT membrane potential, employed immunoblotting to examine the expression of phosphor‐NCC (pNCC) and total NCC (tNCC), and conducted renal clearance method to measure thiazide‐sensitive renal sodium excretion in Kcnj16 +/+ (WT) mice and Kcnj16 −/− mice (Kir5.1 KO). Results We confirmed the previous finding that HS decreased the basolateral K conductance of the DCT, depolarized the DCT membrane, and inhibited the expression of pNCC and tNCC in WT mice. In contrast, LS intake increased the basolateral K conductance, hyperpolarized DCT membrane, and augmented expression of pNCC and tNCC in WT mice. The deletion of Kir5.1 not only increased the basolateral K (Kir4.1) conductance in the DCT and also abolished the inhibitory effect of HS on the basolateral Kir4.1 activity. Also, LS intake did not further stimulate the basolateral Kir4.1 of the DCT. The expression of pNCC and tNCC was upregulated in Kir5.1 KO mice in comparison to WT. Furthermore, neither HS nor LS had an effect on NCC expression in Kir5.1‐deficient mice, suggesting the role of Kir5.1 in mediating the inhibitory effect of HS on NCC expression. Renal clearance experiments also showed that the deletion of Kir5.1 not only augmented the thiazide‐induced natriuresis but also abolished the inhibitory effect of HS on the thiazide‐induced natriuresis in Kir5.1 KO mice. Conclusion Kir5.1 plays an important role in mediating the inhibitory effect of HS intake on the basolateral K channel activity in the DCT and NCC activity/expression. Support or Funding Information NIH‐DK115366