Objective: 

So far, the KCNT family of potassium channels has mainly been investigated in neuronal tissue although the two members, KCNT1 and KCNT2 are additionally expressed in the kidney and other tissues. KCNT K⁺ channels are regulated by intracellular Na⁺ concentration and this might open an interesting perspective on the role of these channels in epithelial ion transport regulation, either under physiological or pathophysiological conditions. We investigated KCNT2 knockout animals (KO) and their respective wild type litter mates (WT) for their phenotype, in particular salt and water homeostasis.

Methods: 

Male (6 WT, 5 KO) and female (7 WT, 7 KO) animals were investigated separately for three days on metabolic cages. At day three, animals were sacrificed and samples (blood, urine) were analysed. In addition, 9–10 animals of each group were investigated for metabolic parameters under normal housing conditions. All animals were at the age of 37–40 weeks

Results: 

KO were viable and showed no obvious gross anatomic abnormalities. However, female KO weighed more in relation to their body length compared to their female WT (body mass index: 3.5±0.1 in KO vs. 3.1±0.1 in WT). KO and WT male animals showed similar values (3.7±0.1 in both genotypes). Plasma glucose concentrations were comparable between groups but plasma cholesterol was elevated in female KO (95±7 mg/dl) vs. female WT (56±4 mg/dl). Metabolic cage experiments in all mice led to transient stress. Water and food consumption showed an initial reduction and recovery within the three days of the experiment. Plasma sodium concentrations were still slightly elevated at day 3 in all groups. However, compared to WT, female KO retained their low water intake and, moreover, decreased their urinary flow rate at day 2 (0.9±0.2 vs. 1.4±0.2 ml/24h) and day 3 (1.1±0. vs. 1.7±0.2 ml/24h), respectively. In addition, creatinine clearance in these animals was reduced at day 3 by 33%. There were no differences in fractional electrolyte excretion values, indicating normal tubular function in KO.

Conclusion: 

Phenotype of KCNT2 deficiency in mice showed strong gender differences mostly affecting female animals. Data indicate alterations in lipid metabolism and a disturbed stress resistance in female KO.