Deletion of Kir5.1 Impairs Renal Ability to Excrete Potassium During Increased Dietary Potassium Intake
BACKGROUND: The basolateral potassium channel in the distal convoluted tubule (DCT), comprising the inwardly rectifying potassium channel Kir4.1/Kir5.1 heterotetramer, plays a key role in mediating the effect of dietary potassium intake on the thiazide-sensitive NaCl cotransporter (NCC). The role of Kir5.1 (encoded by Kcnj16) in mediating effects of dietary potassium intake on the NCC and renal potassium excretion is unknown. METHODS: We used electrophysiology, renal clearance, and immunoblotting to study Kir4.1 in the DCT and NCC in Kir5.1 knockout (Kcnj16(-/-) ) and wild-type (Kcnj16(+/+) ) mice fed with normal, high, or low potassium diets. RESULTS: We detected a 40-pS and 20-pS potassium channel in the basolateral membrane of the DCT in wild-type and knockout mice, respectively. Compared with wild-type, Kcnj16(-/-) mice fed a normal potassium diet had higher basolateral potassium conductance, a more negative DCT membrane potential, higher expression of phosphorylated NCC (pNCC) and total NCC (tNCC), and augmented thiazide-induced natriuresis. Neither high- nor low-potassium diets affected the basolateral DCT's potassium conductance and membrane potential in Kcnj16(-/-) mice. Although high potassium reduced and low potassium increased the expression of pNCC and tNCC in wild-type mice, these effects were absent in Kcnj16(-/-) mice. High potassium intake inhibited and low intake augmented thiazide-induced natriuresis in wild-type but not in Kcnj16(-/-) mice. Compared with wild-type, Kcnj16(-/-) mice with normal potassium intake had slightly lower plasma potassium but were more hyperkalemic with prolonged high potassium intake and more hypokalemic during potassium restriction. CONCLUSIONS: Kir5.1 is essential for dietary potassium's effect on NCC and for maintaining potassium homeostasis.
Wu, P., Gao, Z., Zhang, D., Su, X., Wang, W., & Lin, D. (2019). Deletion of Kir5.1 Impairs Renal Ability to Excrete Potassium During Increased Dietary Potassium Intake. Journal of the American Society of Nephrology, 30 (8), 1425-1438. https://doi.org/10.1681/ASN.2019010025.