Distal tubule basolateral potassium channels: cellular and molecular mechanisms of regulation

Multiple clinical and translational evidence support benefits of high potassium diet; however, there many uncertainties underlying the molecular and cellular mechanisms determining effects of dietary potassium. Kir4.1 and Kir5.1 proteins form a functional heteromer (Kir4.1/Kir5.1), which is the primary inwardly rectifying potassium channel on the basolateral membrane of both distal convoluted tubule (DCT) and the collecting duct principal cells. The purpose of this mini-review is to summarize latest advances in our understanding of the evolution, physiological relevance and mechanisms controlling these channels.

Kir4.1 and Kir5.1 channels play a critical role in determining electrolyte homeostasis in the kidney and blood pressure, respectively. It was reported that Kir4.1/Kir5.1 serves as potassium sensors in the distal nephron responding to variations in dietary intake and hormonal stimuli. Global and kidney specific knockouts of either channel resulted in hypokalemia and severe cardiorenal phenotypes. Furthermore, knock out of Kir5.1 in Dahl salt-sensitive rat background revealed the crucial role of the Kir4.1/Kir5.1 channel in salt-induced hypertension.

Here, we focus on reviewing novel experimental evidence of the physiological function, expression and hormonal regulation of renal basolateral inwardly rectifying potassium channels. Further investigation of molecular and cellular mechanisms controlling Kir4.1 and Kir4.1/Kir5.1-mediating pathways and development of specific compounds targeting these channels function is essential for proper control of electrolyte homeostasis and blood pressure.