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The function and regulation of basolateral Kir4.1 and Kir4.1/Kir5.1 in renal tubules

XIAO Yu, MENG Xin-Xin, ZHANG Hao, GUO Xi-Wen, GU Rui-Min^*

Department of Pharmacology, Harbin Medical University, Harbin 150081, China

Abstract

Basolateral inwardly-rectifying K+ channels (Kir) play an important role in the control of resting membrane potential and transepithelial voltage, thereby modulating water and electrolyte transport in the distal part of nephron. Kir4.1 and Kir4.1/Kir5.1 heterotetramer are abundantly expressed in the basolateral membrane of late thick ascending limb (TAL), distal convoluted tubule (DCT), connecting tubule (CNT) and cortical collecting duct (CCD). Loss-of-function mutations in KCNJ10 cause EAST/SeSAME syndrome in humans associated with epilepsy, ataxia, sensorineural deafness and water-electrolyte metabolism imbalance, which is characterized by salt wasting, hypomagnesaemia, hypokalaemia and metabolic alkalosis. In contrast, mice lacking Kir5.1 have severe renal phenotype apart from hypokalaemia such as high chlorine metabolic acidosis and hypercalcinuria. The genetic knockout or functional inhibition of Kir4.1 suppresses Na-Cl cotransporter (NCC) expression and activity in the DCT. However, the downregulation of Kir4.1 increases epithelial Na+ channel (ENaC) expression in the collecting duct. Recently, factors regulating expression and activity of Kir4.1 and Kir4.1/Kir5.1 were identified, such as cell acidification, dopamine, insulin and insulin-like growth factor-1. The involved mechanisms include PKC, PI3K, Src family protein tyrosine kinases and WNK-SPAK signal transduction pathways. Here we review the progress of renal tubule basolateral Kir, and mainly discuss the function and regulation of Kir4.1 and Kir4.1/Kir5.1.

Key words: kidney tubule; Kir4.1; Kir4.1/Kir5.1; sodium-chloride cotransporter

Received: 2018-06-05　　Accepted: 2018-11-19

Corresponding author: 谷瑞民　　E-mail: ruimingu2916@163.com

DOI: 10.13294/j.aps.2018.0086

Citing This Article：

XIAO Yu, MENG Xin-Xin, ZHANG Hao, GUO Xi-Wen, GU Rui-Min. The function and regulation of basolateral Kir4.1 and Kir4.1/Kir5.1 in renal tubules. Acta Physiol Sin 2018; 70 (6): 600-606 (in Chinese with English abstract).