Abstract
The aim of this mini review is to provide an overview regarding the role of inwardly rectifying potassium channel 4.1 (Kir4.1)/Kir5.1 in regulating renal K+ excretion. Deletion of Kir4.1 in the kidney inhibited thiazide-sensitive NaCl cotransporter (NCC) activity in the distal convoluted tubule (DCT) and slightly suppressed Na-K-2Cl cotransporter (NKCC2) function in the thick ascending limb (TAL). Moreover, increased dietary K+ intake inhibited, whereas decreased dietary K+ intake stimulated, the basolateral potassium channel (a Kir4.1/Kir5.1 heterotetramer) in the DCT. The alteration of basolateral potassium conductance is essential for the effect of dietary K+ intake on NCC because deletion of Kir4.1 in the DCT abolished the effect of dietary K+ intake on NCC. Since potassium intake-mediated regulation of NCC plays a key role in regulating renal K+ excretion and potassium homeostasis, the deletion of Kir4.1 caused severe hypokalemia and metabolic alkalosis under control conditions and even during increased dietary K+ intake. Finally, recent studies have suggested that the angiotensin II type 2 receptor (AT2R) and bradykinin-B2 receptor (BK2R) are involved in mediating the effect of high dietary K+ intake on Kir4.1/Kir5.1 in the DCT.
Highlights
Potassium (Kϩ) is critical for maintaining cellular function
Renal phenotype of loss-of-function mutations of Kir4.1 in the kidney is reminiscent of Gitelman syndrome, characterized by defective NCC function in the distal convoluted tubule (DCT) [2]
We observed that AT2R inhibition significantly increased basolateral potassium conductance in the DCT, hyperpolarized the DCT membrane, and augmented NCC activity
Summary
Renal phenotype of loss-of-function mutations of Kir4.1 in the kidney is reminiscent of Gitelman syndrome, characterized by defective NCC function in the DCT [2]. Understanding the regulation of Kir4.1/Kir5.1 in the kidney should shed light on the regulatory mechanism of overall Kϩ excretion
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