Key result
Targeted Kcne2 gene deletion in mice increased choroid plexus epithelium outward K+ current 2-fold, hyperpolarized the membrane by 9 ± 2 mV, and increased CSF chloride concentration by 14%.
Why the study?
Does Kcne2 gene deletion alter choroid plexus epithelium function and cerebrospinal fluid composition in mice?
Does Kcne2 gene deletion alter choroid plexus epithelium function and cerebrospinal fluid composition in mice?
KCNE2 regulates KCNQ1 and KCNA3 in the choroid plexus epithelium, influencing blood-CSF anion flux and maintaining normal CSF composition.
Kcne2 deletion alters mouse choroid plexus function and CSF composition; leaves open its role in human CSF regulation.
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 μM) and margatoxin (10 μM) 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.
No takes yet. Share an insight, caveat, or question.
Roepke et al. (2011) studied this question. Kcne2 gene deletion vs. Wild-type mice was evaluated on Choroid plexus epithelium outward K(+) current, membrane polarization, and CSF [Cl(-)]. Targeted Kcne2 gene deletion in mice increased choroid plexus epithelium outward K+ current 2-fold, hyperpolarized the membrane by 9 ± 2 mV, and increased CSF chloride concentration by 14%.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: