K + homeostasis is maintained with knockdown of big‐conductance K + channel in principal cells of connecting tubule/collecting duct

Big‐conductance K + (BK) channels are expressed in principal cells (PC) and intercalated cells of the kidney and contribute to K + homeostasis and flow‐induced K + secretion. To define the role of BK channels in PC, we generated mice with conditionally inactivated BK channels in PC of the connecting tubule/collecting duct (AQP2:Cre; BK loxloxCre ). Cre negative BK loxlox mice served as controls (Con). On standard diet (Teklad 7001), Plasma Na + (Con vs BK loxloxCre : 150±0.4 vs 150±0.4 mmol/l), K + (4.4±0.1 vs 4.3±0.1 mmol/l), pH (7.4±0.04 vs 7.4±0.04), and hematocrit (49±0.4 vs 50±0.5 %) were not different between genotypes. Systolic blood pressure and heart rate, determined by tail cuff, were comparable between genotypes (Con: 113±2 mmHg and 623±16 min −1 , BK loxloxCre : 116±2 mmHg and 647±13 min −1 ). Spontaneous urine collections showed similar urine osmolality in Con and BK loxloxCre (2041±87 vs 1950±85 mmol/kg). However, urinary K + /Na + ratio was significantly higher in BK loxloxCre vs Con (1.49±0.07 vs. 1.17±0.07, P<0.05 ) due to lower urinary Na + /creatinine (crea) in BK loxloxCre vs Con (21.7±1.3 vs. 25.4±1.1, mmol/mmol P<0.05 ), while urinary K + /crea was not different (31.9±1.8 vs 29.6±1.6 mmol/mmol). Our data indicate that under control diet conditional knockdown of BK channels in PC of the connecting tubule/collecting duct reduces Na + excretion while K + homeostasis is maintained.