Objective · To investigate the effect of extracellular potassium (K+) concentration on the activities of sodium chloride co-transporter (NCC) and large conductance Ca2+-activated K+ channel (BK) in distal renal tubule of mice. Methods · Six specific pathogen free (SPF) C57BL/6 mice aged 8 to 10 weeks were sacrificed, and the kidney slices were made with previously reported method. Then, these slices were incubated randomly in normal K+, high K+, BaCl2 and RbCl solutions, respectively. The abundance and phosphorylation level of NCC in kidney slices at different K+ concentrations and different time courses were detectedWestern blotting. The overall and membrane s of BK in kidney slices were also detected after incubation with different K+ solutions for 2 h. Results · Compared with normal K+ solution, NCC phosphorylation level was significantly decreased after incubation with high K+ solution for 5, 15, 30 min (all P<0.05), and NCC phosphorylation level was also decreased after intervention with K+ channel inhibitor Ba2+ or Rb+ (both P<0.05). After the treatment with high K+ solution for 2 h, neither the overall cell of BKα subunit and β4 subunit, nor membrane of BKα subunit was found significant changes compared with normal K+ incubation. Conclusion · High K+ can directly down-regulate NCC phosphorylation level, which may be preparation for kaliuresis of the downstream tubule of distal convoluted tubule.