Regulation and function of potassium channels in aldosterone-sensitive distal nephron

Abstract

K channels in the aldosterone-sensitive distal nephron (ASDN) participate in generating cell membrane potential and in mediating K secretion. The aim of the review is to provide an overview of the recent development regarding physiological function of the K channels and the novel factors which modulate the K channels of the ASDN. Genetic studies and transgenic mouse models have revealed the physiological function of basolateral K channels including inwardly rectifying K channel (Kir) and Ca-activated big-conductance K channels in mediating salt transport in the ASDN. A recent study shows that intersectin is required for mediating with-no-lysine kinase (WNK)-induced endocytosis. Moreover, a clathrin adaptor, autosomal recessive hypercholesterolemia (ARH), and an aging-suppression protein, Klothe, have been shown to regulate the endocytosis of renal outer medullary potassium (ROMK) channel. Also, serum-glucocorticoids-induced kinase I (SGK1) reversed the inhibitory effect of WNK4 on ROMK through the phosphorylation of WNK4. However, Src-family protein tyrosine kinase (SFK) abolished the effect of SGK1 on WNK4 and restored the WNK4-induced inhibition of ROMK. Basolateral K channels including big-conductance K channel and Kir4.1/5.1 play an important role in regulating Na and Mg transport in the ASDN. Apical K channels are not only responsible for mediating K excretion but they are also involved in regulating transepithelial Mg absorption. New factors and mechanisms by which hormones and dietary K intake regulate apical K secretory channels expand the current knowledge regarding renal K handling.