Blood-brain barrier KCa3.1 Channels: Evidence for a role in brain na uptake and edema in ischemic stroke

Yi-Je Chen, Breanna K. Wallace, Natalie Yuen, David P. Jenkins, Heike Wulff, Martha E O'Donnell

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Background and Purpose-KCa3.1, a calcium-activated potassium channel, regulates ion and fluid secretion in the lung and gastrointestinal tract. It is also expressed on vascular endothelium where it participates in blood pressure regulation. However, the expression and physiological role of KCa3.1 in blood-brain barrier (BBB) endothelium has not been investigated. BBB endothelial cells transport Na and Cl from the blood into the brain transcellularly through the co-operation of multiple cotransporters, exchangers, pumps, and channels. In the early stages of cerebral ischemia, when the BBB is intact, edema formation occurs by processes involving increased BBB transcellular Na transport. This study evaluated whether KCa3.1 is expressed on and participates in BBB ion transport.

Methods-The expression of KCa3.1 on cultured cerebral microvascular endothelial cells, isolated microvessels, and brain sections was evaluated by Western blot and immunohistochemistry. Activity of KCa3.1 on cerebral microvascular endothelial cells was examined by K flux assays and patch-clamp. Magnetic resonance spectroscopy and MRI were used to measure brain Na uptake and edema formation in rats with focal ischemic stroke after TRAM-34 treatment.

Results-KCa3.1 current and channel protein were identified on bovine cerebral microvascular endothelial cells and freshly isolated rat microvessels. In situ KCa3.1 expression on BBB endothelium was confirmed in rat and human brain sections. TRAM-34 treatment significantly reduced Na uptake, and cytotoxic edema in the ischemic brain.

Conclusions-BBB endothelial cells exhibit KCa3.1 protein and activity and pharmacological blockade of KCa3.1 seems to provide an effective therapeutic approach for reducing cerebral edema formation in the first 3 hours of ischemic stroke.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalStroke
Volume46
Issue number1
DOIs
StatePublished - Jan 3 2015

Keywords

  • blood Cbrain barrier
  • brain edema
  • cerebral ischemia
  • KCa3.1 protein, mouse
  • stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

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