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The Disruption of KCNJ10 (Kir4.1) Depolarizes the Membrane Potential of the CNT and Stimulates the Expression of ENaC in the Medullary Collecting Duct
Author(s) -
Su XiaoTong,
Zhang Chengbiao,
Wang Lijun,
Lin DaoHong,
Wang WenHui
Publication year - 2015
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.29.1_supplement.844.7
Subject(s) - medullary cavity , duct (anatomy) , epithelial sodium channel , chemistry , microbiology and biotechnology , anatomy , biology , sodium , organic chemistry
Previous study has demonstrated that the disruption of KCNJ10 decreased the expression of NCC in the distal convoluted tubule (DCT). The aim of the present study is to examine the role of KCNJ10 in contributing to the basolateral K conductance in connecting tubule (CNT) and to investigate the effect of KCNJ10 disruption on ENaC expression using Kcnj10 +/+ and ‐/‐ mice. The patch‐clamp studies detected three types of K channel (23 pS, 40 pS and 60 pS) in the basolateral membrane of the CNT in the WT mice. However, only 23 pS and 60 pS K channels but not the 40 pS K channel were found in the basolateral membrane of the CNT of Kcnj10 ‐/‐ mice, suggesting that KCNJ10 is a key component of the 40 pS K channel in CNT. Moreover, the probability of finding the 23 pS and 60 pS K channel in CNT was the same between the WT and Kcnj10 ‐/‐ mice. To assess the role of KCNJ10 in determining the membrane potential in CNT, we used the perforated patch to measure the K reversal voltage (V Kr ) of CNT as an index of the cell membrane potential. With 5 mM K + in bath and 140 mM K + in pipette, V Kr was ‐69 mV in CNT of WT mice and ‐61 mV in Kcnj 10 ‐/‐ mice. Western blot analysis showed that the disruption of KCNJ10 significantly increased the expression of ENaC a and ENaC b in medulla while it had no effect on ENaC expression in cortex. Immunostaining further confirmed that ENaC expression is increased in the medullary collecting duct but it is unchanged in the cortical collecting duct (CCD). The disruption of KCNJ10 also has no effect on AQP2 expression. We conclude that KCNJ10 is expressed in CNT and CCD and participates in generating the cell membrane potential in CNT. Also, the disruption‐induced stimulation of ENaC expression is a compensation action to the impaired Na transport in DCT.