Ion transport homeostasis in Alpha‐1 AMPK KO mice

Abstract

AMP‐activated kinase (AMPK) regulates cell energy balance by modulating ATP synthesis and consumption. In epithelia, AMPK interacts with and regulate ion transport systems, including CFTR, ENaC and NKCC. We studied renal function and measured blood pressure in mice with genetic deletion of the alpha‐1 catalytic subunit of AMPK (a1KO mice; C57Bl6J background). When fed a standard diet (0.3%NaCl) a1KO mice showed mild antidiuresis (WT=0.053 vs. KO=0.038 mL/d/g bw). No significant differences in glomerular filtration rate, sodium or potassium handling were found. When fed low Na+ (0.02%) or high salt (4%NaCl) diets, a1KO mice achieved ion and water balance. Lack of aversion for the high salt diet in a1KO mice suggested increased sodium appetite. Aldosterone urinary excretion was consistently higher in a1KO mice (WT=0.028 vs. KO=0.037 ng/d/g bw). Telemetric 24h blood pressure records showed significantly lower blood pressure in a1KO mice, especially nocturnal diastolic pressure (WT=93.5 vs. KO=86.1 mmHg). We found that a1KO mice lose water and sodium in their feces compared to wild‐type mice. In the kidney, we observed up‐regulation of the alpha‐2 catalytic subunit, which may provide functional compensation for the loss of alpha‐1 activity. Thus, kidneys from a1KO mice apparently have normal function and may be actually compensating for extra renal water and ion losses.MICIIN Spain BFU2007/62119