Regulation of the voltage-gated K+ channels KCNQ2/3 and KCNQ3/5 by serum- and glucocorticoid-regulated kinase-1

Schuetz, F., Kumar, S., Poronnik, P. and Adams, D. J. (2008) Regulation of the voltage-gated K+ channels KCNQ2/3 and KCNQ3/5 by serum- and glucocorticoid-regulated kinase-1. American Journal of Physiology-Cell Physiology, 295 1: C73-C80. doi:10.1152/ajpcell.00146.2008


Author Schuetz, F.
Kumar, S.
Poronnik, P.
Adams, D. J.
Title Regulation of the voltage-gated K+ channels KCNQ2/3 and KCNQ3/5 by serum- and glucocorticoid-regulated kinase-1
Journal name American Journal of Physiology-Cell Physiology   Check publisher's open access policy
ISSN 0363-6143
Publication date 2008-01-01
Year available 2008
Sub-type Article (original research)
DOI 10.1152/ajpcell.00146.2008
Open Access Status
Volume 295
Issue 1
Start page C73
End page C80
Total pages 8
Editor Drown, D
Reich, M
Place of publication United State
Publisher American Physiological Society
Language eng
Subject C1
110902 Cellular Nervous System
920111 Nervous System and Disorders
Abstract The voltage-gated KCNQ2/3 and KCNQ3/5 K+ channels regulate neuronal excitability. We recently showed that KCNQ2/3 and KCNQ3/5 channels are regulated by the ubiquitin ligase Nedd4-2. Serum- and glucocorticoid-regulated kinase-1 (SGK-1) plays an important role in regulation of epithelial ion transport. SGK-1 phosphorylation of Nedd4-2 decreases the ability of Nedd4-2 to ubiquitinate the epithelial Na+ channel, which increases the abundance of channel protein in the cell membrane. In this study, we investigated the mechanism(s) of SGK-1 regulation of M-type KCNQ channels expressed in Xenopus oocytes. SGK-1 significantly upregulated the K+ current amplitudes of KCNQ2/3 and KCNQ3/5 channels similar to 1.4- and similar to 1.7-fold, respectively, whereas the kinase-inactive SGK-1 mutant had no effect. The cell surface levels of KCNQ2-hemagglutinin/3 were also increased by SGK-1. Deletion of the KCNQ3 channel COOH terminus in the presence of SGK-1 did not affect the K+ current amplitude of KCNQ2/3/5-mediated currents. Coexpression of Nedd4-2 and SGK-1 with KCNQ2/3 or KCNQ3/5 channels did not significantly alter K+ current amplitudes. Only the Nedd4-2 mutant (S448A)Nedd4-2 exhibited a significant downregulation of the KCNQ2/3/5 K+ current amplitudes. Taken together, these results demonstrate a potential mechanism for regulation of KCNQ2/3 and KCNQ3/5 channels by SGK-1 regulation of the activity of the ubiquitin ligase Nedd4-2.
Keyword KCNQ channel
M current
potassium channel
ubiquitin ligase
Xenopus
oocyte
CELL-SURFACE EXPRESSION
EPITHELIAL NA+ CHANNEL
NEURONAL EXCITABILITY
HIPPOCAMPAL-NEURONS
POTASSIUM CHANNELS
UBIQUITIN LIGASE
SYMPATHETIC
NEURONS
KCNQ/M-CURRENTS
SODIUM-CHANNELS
KV7 CHANNELS
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 16 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 18 Mar 2009, 22:04:27 EST