The K⁺ channel β subunit KCNE1 plays a role in proximal tubule function, maintaining electrogenic transport. KCNE1 knockout (KO) mice show increased urinary excretion of Na⁺, glucose and fluid (Vallon, 2001). KCNE1 regulates KCNQ1, which is found in the kidney. However, the renal response in KCNQ1 KO mice is different (Vallon, 2005). In addition, a recent report indicated a distal location for KCNQ1 (Zheng, 2007). The aim of this study was to examine the renal response to chromanol 293B, a KCNQ1 inhibitor, comparing responses in wildtype (WT) and KCNE1 KO mice. Adult WT and KCNE1 KO mice were anaesthetised initially with Na⁺ thiopentone (100 mg/kg) and anaesthesia maintained with ketamine (10mg/kg) and xylazine (1.5 mg/kg), all intra peritoneal injections. They were then surgically prepared for renal clearance measurements. Animals received an intravenous infusion of 2.25g/dl BSA in isotonic saline. After surgery, chromanol 293B (12 µmol/kg/hr) or clofilium (K⁺ channel inhibitor, 9 µmol/kg/hr) were administered. After 45 minutes equilibration urine was collected over 60 minutes. 3H-inulin was infused to allow determination of GFR. Controls received an equivalent dose of vehicle (DMSO). At the end of the collection period, a terminal blood sample was taken to obtain plasma. Statistical significance was assessed using ANOVAs and treatment tests, with significance assumed at the 5% level. Knockout of KCNE1 increased urine flow and the fractional excretion (FE) of Na⁺ and Cl^– (Table 1). The FEglucose was unaffected in KO animals, 0.30 ± 0.06% versus 0.26 ± 0.06% in WT and KO, respectively. Infusion of chromanol 293B in WT mice mimicked the response observed in KO animals, while chromanol was without effect in KO mice. In contrast, clofilium increased the FE of Na⁺ and Cl^– in WT and KO animals. There was no effect on urine flow, probably due to a reduced GFR in the clofilium treated mice. These data indicate that KCNE1 regulates a chromanol 293B sensitive K⁺ channel in renal tubules. Given the previous work on KCNE1, the location of this channel is likely to be the proximal tubule, although further work is needed to confirm both channel location and identity.