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Kir5.1 is essential for the effect of dietary potassium intake on the basolateral K channels and Na‐Cl cotransporter (NCC) in the distal convoluted tubule (DCT)
Author(s) -
Lin Daohong,
Wu Peng,
Gao ZhongXiuzi,
Wang Wenhui,
Su Xiaotong,
Zhang Dandan
Publication year - 2019
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.2019.33.1_supplement.862.1
Subject(s) - distal convoluted tubule , chemistry , cotransporter , endocrinology , medicine , symporter , renal physiology , kidney , homeostasis , reabsorption , epithelial polarity , transporter , biochemistry , sodium , membrane , organic chemistry , gene
The basolateral potassium (K + ) channel is composed of Kir4.1 and Kir5.1 in the distal convoluted tubule (DCT). Kir4.1/Kir5.1 heterotetramer is mainly responsible for providing basolateral K + conductance in the DCT and plays a key role in mediating the effect of dietary K + intake on thiazide‐sensitive Na‐Cl cotransporter (NCC) by regulating DCT membrane potential. The notion that the Kir4.1/5.1 heterotetramer is essential for maintaining K + homeostasis is supported by the findings that the deletion of Kir4.1 in the kidney caused severe renal K + wasting and that the mice were hypokalemic. Our previous study demonstrated that Kir5.1 plays a role in facilitating the ubquitination of Kir4.1 and that the deletion of Kir5.1 increased the basolateral K + conductance in the DCT, suggesting the role of Kir5.1 in regulating Kir4.1 activity. The aim of the present study is to test the hypothesis that deletion of Kir5.1 should impair the renal regulatory ability for controlling a proper K + excretion. We detected a 20 pS K + channel in the basolateral membrane of the DCT in Kcnj16 −/− mice and the mice had higher basolateral K + conductance and more negative membrane potential in the DCT than those of WT littermates. Immunoblotting showed that the expression of phosphorylated NCC (pNCC) and total NCC (tNCC) was higher in Kcnj16 −/− mice than in WT littermates. Renal Na clearance study demonstrated that the thiazide‐induced natriuresis was augmented in Kcnj16 −/− mice. Moreover, neither high K + (HK) nor low K + (LK) intake had an effect on the basolateral K + conductance of the DCT and membrane potential. HK reduced while LK increased the expression of pNCC and tNCC in WT mice but this effect was either absent or significantly attenuated in Kcnj16 −/− mice. Renal clearance study further demonstrated that thiazide‐induced natriuretic effect in Kcnj16 −/− mice on HK diet or LK diet was not significantly different from those on normal K + diet. While plasma K + concentration in Kcnj16 −/− mice on normal K + diet was still normakalemia but lower than WT mice, Kcnj16 −/− mice were more hyperkalemic than WT littermates with prolonged HK intake and more hypokalemic after 7‐day LK intake. We conclude that Kir5.1 is essential for the effect of dietary K intake on the basolateral K + channels of the DCT and NCC. Support or Funding Information NIH‐R01DK115366 (DHL)Effect of dietary K+ on renal Na+ excretion (ENa) is compromised in Kir5.1 KO miceThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .