Tong Wang
Yale School of Medicine-Yale University, USA
Title: Renal outer medullary potassium channel knockout models reveal bartter’s syndrome and dysfunction of potassium homeostasis
Biography
Biography: Tong Wang
Abstract
The renal outer medullary potassium channel (ROMK) is an ATP-sensitive inward-rectifier potassium channel (Kir1.1 or KCNJ1) highly expressed in the kidney. We have demonstrated that ROMK -/- mice show a similar phenotype to Bartter’s syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity in the thick ascending limb (TAL). Patch clamp studies showed that ROMK is required to form both the small-conductance (30-pS, SK) K and the 70-pS (IK) K channels in the kidney. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in ROMK 1 by selective deletion of the ROMK 1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity and localization under normal and high K intake. Unlike ROMK -/- mice, there was no Bartter’s phenotype with reduced NKCC2 activity and increased NCC expression in ROMK1-/- mice. The SK activity showed no difference of channel properties or gating in the collecting tubule (CCD) between ROMK1+/+ and ROMK1-/- mice. High K intake increased SK channel number per patch and the ROMK channel intensity in the apical membrane of the CCD in ROMK1+/+, but such regulation was diminished with significant hyperkalemia in ROMK1-/- mice. These results are consistent with previous studies that ROMK1 does not localize in the TAL, and that ROMK1 is a key target of PTK-mediated ROMK trafficking in response to K+ intake.