Abstract
The kidney maintains systemic potassium (K+) balance through energy-intensive epithelial transport processes. Under K+-restricted conditions, kidney epithelial cells proliferate to accommodate profound increases in transport. Tissue reorganization to minimize systemic K+ loss is essential for survival, yet metabolic details remain obscure. Here, we demonstrate that the most-activated kidney pathways under low K+ conditions are those governing metabolism, including carbohydrate- and glutamine-based processes and fatty acid synthesis. We identify that reduced K+ intake stimulates glycolytic flux in the renal cortex to increase amino acid abundance, de novo fatty acid synthesis, and organ expansion. Using a novel mouse model harboring a dominant-negative Kir5.1 channel, we show that each of these steps is dependent on intact basolateral Kir channel flux to initiate rapid kidney growth. Results identify details of a low K+-simulated anabolic kidney program requiring Kir channel function and highlight a therapeutic role for targeting Kir channels to modulate cell physiology and metabolism.
Keywords:
Cellular physiology; Metabolic flux analysis; Technical aspects of cell biology.