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Role and mechanisms of regulation of the basolateral K ir 4.1/K ir 5.1K + channels in the distal tubules
Author(s) -
Palygin O.,
Pochynyuk O.,
Staruschenko A.
Publication year - 2017
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12703
Subject(s) - distal convoluted tubule , epithelial polarity , intercalated cell , homeostasis , biology , nephron , microbiology and biotechnology , reabsorption , inward rectifier potassium ion channel , endocrinology , medicine , apical membrane , epithelial sodium channel , sgk1 , kidney , chemistry , ion channel , biochemistry , kinase , receptor , sodium , cell , membrane , organic chemistry
Epithelial K + channels are essential for maintaining electrolyte and fluid homeostasis in the kidney. It is recognized that basolateral inward‐rectifying K + (K ir ) channels 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 and collecting duct. Monomeric K ir 4.1 (encoded by Kcnj10 gene) and heteromeric K ir 4.1/K ir 5.1 (K ir 4.1 together with K ir 5.1 ( Kcnj16 )) channels are abundantly expressed at the basolateral membranes of the distal convoluted tubule and the cortical collecting duct cells. Loss‐of‐function mutations in KCNJ 10 cause EAST /Se SAME tubulopathy in humans associated with salt wasting, hypomagnesaemia, metabolic alkalosis and hypokalaemia. In contrast, mice lacking K ir 5.1 have severe renal phenotype that, apart from hypokalaemia, is the opposite of the phenotype seen in EAST /Se SAME syndrome. Experimental advances using genetic animal models provided critical insights into the physiological role of these channels in electrolyte homeostasis and the control of kidney function. Here, we discuss current knowledge about K + channels at the basolateral membrane of the distal tubules with specific focus on the homomeric K ir 4.1 and heteromeric K ir 4.1/K ir 5.1 channels. Recently identified molecular mechanisms regulating expression and activity of these channels, such as cell acidification, dopamine, insulin and insulin‐like growth factor‐1, Src family protein tyrosine kinases, as well as the role of these channels in NCC ‐mediated transport in the distal convoluted tubules, are also described.