Life and death of the distal nephron: WNK4 and NCC as major players.

Abstract

Missense mutations in the WNK4 gene lead to the development of familial hyperkalemic hypertension, a rare form of human hypertension. It was shown in vitro that WNK4 regulates the surface expression and activity of a number of ion channels and transporters. The in vivo analysis of wild-type and mutant WNK4 overexpression in transgenic mice models demonstrated that this serine-threonine kinase controls ion handling in the kidney mainly, and probably exclusively, through the regulation of the Na-Cl contransporter NCC activity.