AMPK is a serine threonine kinase whose activation and protein levels are increased when a cell is metabolically stressed. Studies were done to analyze AMPK activation on Madin Darby Canine Kidney Clone 7 (MDCK-C7) cells, which are a model of the principal cells of the distal tubule. This portion of the nephron is under fine hormonal control to reabsorb and secrete ions between blood and filtrate and maintain electrolyte homeostasis. Anti-diuretic hormone (ADH) produces a tri-phasic response in the MDCK-C7 cell line which includes anion secretion through the cystic fibrosis transmembrane regulator (CFTR) and sodium reabsorption through the epithelial sodium channel (ENaC). Ussing style electrophysiology was used to measure short circuit current which is directly proportional to net ion flux across the MDCK-C7 epithelial layer. AICAR, (1mM) an AMPK activator was added to the serosal and apical bathing media of confluent cultures and allowed to preincubate for 15 minutes, 2 hours, or 18 to 24 hours before anti-diuretic hormone was added. The specific ENaC blocker amiloride was added 30 minutes after ADH to quantitate sodium reabsorption. In long term AICAR treated MDCK-C7 monolayers, anion secretion through CFTR was inhibited.