Disruption of Kcnj10 in mice eliminated the 40-pS basolateral K channel, decreased membrane potential negativity, and diminished apical NCC expression in the early distal convoluted tubule.
Does Kcnj10 disruption affect basolateral K conductance and apical NCC expression in the DCT1 of mice?
Kcnj10 plays a dominant role in determining basolateral K conductance and membrane potential in DCT1, which in turn regulates apical NCC expression.
The renal phenotype induced by loss-of-function mutations of inwardly rectifying potassium channel (Kir), Kcnj10 (Kir4.1), includes salt wasting, hypomagnesemia, metabolic alkalosis and hypokalemia. However, the mechanism by which Kir.4.1 mutations cause the tubulopathy is not completely understood. Here we demonstrate that Kcnj10 is a main contributor to the basolateral K conductance in the early distal convoluted tubule (DCT1) and determines the expression of the apical Na-Cl cotransporter (NCC) in the DCT. Immunostaining demonstrated Kcnj10 and Kcnj16 were expressed in the basolateral membrane of DCT, and patch-clamp studies detected a 40-pS K channel in the basolateral membrane of the DCT1 of p8/p10 wild-type Kcnj10(+/+) mice (WT). This 40-pS K channel is absent in homozygous Kcnj10(-/-) (knockout) mice. The disruption of Kcnj10 almost completely eliminated the basolateral K conductance and decreased the negativity of the cell membrane potential in DCT1. Moreover, the lack of Kcnj10 decreased the basolateral Cl conductance, inhibited the expression of Ste20-related proline-alanine-rich kinase and diminished the apical NCC expression in DCT. We conclude that Kcnj10 plays a dominant role in determining the basolateral K conductance and membrane potential of DCT1 and that the basolateral K channel activity in the DCT determines the apical NCC expression possibly through a Ste20-related proline-alanine-rich kinase-dependent mechanism.
Zhang et al. (Mon,) conducted a other in Kcnj10 (Kir4.1) loss-of-function tubulopathy. Kcnj10 knockout vs. Wild-type Kcnj10(+/+) was evaluated on Basolateral K conductance, membrane potential, and apical NCC expression in DCT1. Disruption of Kcnj10 in mice eliminated the 40-pS basolateral K channel, decreased membrane potential negativity, and diminished apical NCC expression in the early distal convoluted tubule.
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