K+–Mediated Regulation of Distal Convoluted Tubule Na/Cl Cotransporter Phosphorylation During Angiotensin II–Induced Hypertension
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The thiazide-sensitive Na/Cl cotransporter NCC mediates NaCl reabsorption by the distal convoluted tubule (DCT) playing an important role in Na homeostasis and blood pressure regulation. In addition, the DCT is involved in maintaining K+ homeostasis by controlling the amount of K+ secreted into the lumen through the apical channel ROMK (renal outer medulla K+ channel).1
NH2-terminal NCC phosphorylation by SPAK (STE20-related proline–alanine rich kinase) kinases is known to stimulate NCC activity. It is well established that chronically elevated angiotensin II (Ang II) increases NCC phosphorylation, and this thought to be mediated in part by activation of SPAK kinases. Several lines of evidence indicate that WNK (with-no-lysine kinase) kinases are upstream of SPAK and involved in Ang II–induced stimulation of NCC phosphorylation. However, recent data point to an important role of plasma potassium in the regulation of NCC phosphorylation that may override NCC regulation by hormones and dietary salt. For example, acutely increasing plasma K+ in rats decreased …