KCNE1 regulates a chromanol‐sensitive pathway in mouse kidney

Abstract

KCNE1 is known to regulate the chromanol 293B – and clofilium – sensitive K+ channel KCNQ1 in a number of tissues. However, KCNE1 and KCNQ1 knockout mice have different renal phenotypes, suggesting that KCNE1 may not regulate KCNQ1 in the renal system. The aim of the current study was to examine the effect of these KCNQ1 inhibitors in wildtype (WT) and KCNE1 knockout (KO) mice using in vivo renal clearance approaches. KCNE1 KO mice had an increased fractional excretion (FE) of Na+, Cl−, and water (FE Na was 2.1 ± 0.3 % n = 8 vs 3.3 ± 0.4 % n = 9, in WT and KO, respectively). This was mimicked in WT mice by chromanol 293B (FENa = 4.2 ± 0.2 % n = 6), while chromanol was without additional effect in KCNE1 KO animals (FENa = 3.7 ± 0.4 % n = 9). In contrast, clofilium increased the FE of Na+, Cl− and water in both WT and KO mice. The FE Na was 3.9 ± 0.4 % n = 10 and 4.7 ± 0.4 % n = 9, in WT and KO animals, respectively. Taken together these data suggest that KCNE1 regulates a chromanol – sensitive pathway in the kidney. Consistent with the data comparing KCNQ1 and KCNE1 knockout mice, the response to clofilium in knockout animals would suggest that it is not attributable to KCNQ1.