SPAK Sensitive Regulation of the Epithelial Na Channel ENaC.

Abstract:

BACKGROUND/AIMS:The WNK-dependent STE20/SPS1-related proline/alanine-rich kinase SPAK participates in the regulation of NaCl and Na(+),K(+),2Cl(-) cotransport and thus renal salt excretion. The present study explored whether SPAK has similarly the potential to regulate the epithelial Na(+) channel (ENaC). METHODS:ENaC was expressed in Xenopus oocytes with or without additional expression of wild type SPAK, constitutively active (T233E)SPAK, WNK insensitive (T233A)SPAK or catalytically inactive (D212A)SPAK, and ENaC activity estimated from amiloride (50 µM) sensitive current (Iamil) in dual electrode voltage clamp experiments. Moreover, Ussing chamber was employed to determine Iamil in colonic tissue from wild type mice (spak(wt/wt)) and from gene targeted mice carrying WNK insensitive SPAK (spak(tg/tg)). RESULTS:Iamil was observed in ENaC-expressing oocytes, but not in water-injected oocytes. In ENaC expressing oocytes Iamil was significantly increased following coexpression of wild-type SPAK and (T233E)SPAK, but not following coexpression of (T233A)SPAK or (D212A)SPAK. Colonic Iamil was significantly higher in spak(wt/wt) than in spak(tg/tg) mice. CONCLUSION:SPAK has the potential to up-regulate ENaC.

journal_name

Kidney Blood Press Res

authors

Ahmed M,Salker MS,Elvira B,Umbach AT,Fakhri H,Saeed AM,Shumilina E,Hosseinzadeh Z,Lang F

doi

10.1159/000368509

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

335-43

issue

4

eissn

1420-4096

issn

1423-0143

pii

000368509

journal_volume

40

pub_type

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