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J Biol Chem. 2016 Mar 4;291(10):5259-69. doi: 10.1074/jbc.M115.707877. Epub 2016 Jan 4.

Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion.

Author information

1
From the Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520 and ke.dong@yale.edu.
2
From the Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520 and.
3
the Department of Pharmacology, New York Medical College, Valhalla, New York 10595.
4
From the Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520 and tong.wang@yale.edu.

Abstract

Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. 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 Romk1 by selective deletion of the Romk1-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 phenotype with reduced NKCC2 activity and increased NCC expression in Romk1(-/-) mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1(+/+) and Romk1(-/-) mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1(+/+), but such regulation by high K intake was diminished with significant hyperkalemia in Romk1(-/-) mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K(+) secretion in the collecting tubule.

KEYWORDS:

Bartter syndrome; K channel; ROMK isoforms; patch clamp; potassium channel; potassium transport; sodium and potassium homeostasis; sodium transport; transgenic mice

PMID:
26728465
PMCID:
PMC4777858
DOI:
10.1074/jbc.M115.707877
[Indexed for MEDLINE]
Free PMC Article
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