SPAK and OSR1 Dependent Down-Regulation of Murine Renal Outer Medullary K+ Channel ROMK1

被引：23

作者：

Elvira, Bernat ^{[1
]}

Munoz, Carlos ^{[2
,3
]}

Borras, Jose ^{[1
]}

Chen, Hong ^{[1
]}

Warsi, Jamshed ^{[1
]}

Ajay, Sunnant Singh ^{[1
]}

Shumilina, Ekaterina ^{[1
]}

Lang, Florian ^{[1
]}

机构：

[1] Univ Tubingen, Dept Physiol 1, D-72076 Tubingen, Germany

[2] Univ Zurich, Inst Physiol, Zurich, Switzerland

[3] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, Zurich, Switzerland

来源：

KIDNEY & BLOOD PRESSURE RESEARCH | 2014年 / 39卷 / 04期

关键词：

K+ channel; Oxidative stress-responsive kinase 1; Renal tubule; SPS1-related proline/alanine-rich kinase; WNK; BLOOD-PRESSURE; UP-REGULATION; WNK KINASES; HYPERTENSION; POTASSIUM; TRANSPORT; SODIUM; COTRANSPORTERS; SENSITIVITY; MECHANISMS;

D O I：

10.1159/000355812

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

Background/Aims: The kinases SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1) participate in the regulation of the NaCl cotransporter NCC and the Na+,K+,2Cl(-) cotransporter NKCC2. The kinases are regulated by WNK (with-no-K[Lys]) kinases. Mutations of genes encoding WNK kinases underly Gordon's syndrome, a monogenic disease leading to hypertension and hyperkalemia. WNK kinases further regulate the renal outer medullary K+ channel ROMK1. The present study explored, whether SPAK and/or OSR1 have similarly the potential to modify the activity of ROMK1. Methods: ROMK1 was expressed in Xenopus oocytes with or without additional expression of wild-type SPAK, constitutively active (T233E)SPAK, catalytically inactive (D212A)SPAK, wild-type OSR1, constitutively active (T185E)OSR1 and catalytically inactive (D164A)OSR1. Channel activity was determined utilizing dual electrode voltage clamp and ROMK1 protein abundance in the cell membrane utilizing chemiluminescence of ROMK1 containing an extracellular hemagglutinin epitope (ROMK1-HA). Results: ROMK1 activity and ROMK1-HA protein abundance were significantly down-regulated by wild-type SPAK and (T233E)SPAK, but not by (D212A)SPAK. Similarly, ROMK1 activity and ROMK1-HA protein abundance were significantly down-regulated by wild-type OSR1 and (T185E)OSR1, but not by (D164A)OSRl. Conclusion: ROMK1 protein abundance and activity are down-regulated by SPAK and OSR1. Copyright (C) 2014 S. Karger AG, Basel

引用

页码：353 / 360

页数：8

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