KCNE2 forms potassium channels with KCNA3 and KCNQ1 in the choroid plexus epithelium

Item Type:	Article
Title:	KCNE2 forms potassium channels with KCNA3 and KCNQ1 in the choroid plexus epithelium
Creators Name:	Roepke, T.K. and Kanda, V.A. and Purtell, K. and King, E.C. and Lerner, D.J. and Abbott, G.W.
Abstract:	Cerebrospinal fluid (CSF) is crucial for normal function and mechanical protection of the CNS. The choroid plexus epithelium (CPe) is primarily responsible for secreting CSF and regulating its composition by mechanisms currently not fully understood. Previously, the heteromeric KCNQ1-KCNE2 K(+) channel was functionally linked to epithelial processes including gastric acid secretion and thyroid hormone biosynthesis. Here, using Kcne2(-/-) tissue as a negative control, we found cerebral expression of KCNE2 to be markedly enriched in the CPe apical membrane, where we also discovered expression of KCNQ1. Targeted Kcne2 gene deletion in C57B6 mice increased CPe outward K(+) current 2-fold. The Kcne2 deletion-enhanced portion of the current was inhibited by XE991 (10 {minuskel}M) and margatoxin (10 {minuskel}M) but not by dendrotoxin (100 nM), indicating that it arose from augmentation of KCNQ subfamily and KCNA3 but not KCNA1 K(+) channel activity. Kcne2 deletion in C57B6 mice also altered the polarity of CPe KCNQ1 and KCNA3 trafficking, hyperpolarized the CPe membrane by 9 ± 2 mV, and increased CSF [Cl(-)] by 14% compared with wild-type mice. These findings constitute the first report of CPe dysfunction caused by cation channel gene disruption and suggest that KCNE2 influences blood-CSF anion flux by regulating KCNQ1 and KCNA3 in the CPe.
Keywords:	Central Nervous System, Cerebrospinal Fluid, MiRP1, Polarized Trafficking, Ventricles, Animals, Mice
Source:	FASEB Journal
ISSN:	0892-6638
Publisher:	Federation of American Societies for Experimental Biology
Volume:	25
Number:	12
Page Range:	4264-4273
Date:	December 2011
Official Publication:	https://doi.org/10.1096/fj.11-187609
PubMed:	View item in PubMed

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