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Blood brain barrier KCa3.1 channels: evidence for a role in brain Na uptake and edema during ischemic stroke
Author(s) -
Chen Yi-Je Jay,
Yuen Natalie,
Wallace Breanna K,
Wulff Heike,
O'Donnell Martha E
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.695.13
Subject(s) - ischemia , blood–brain barrier , medicine , edema , cerebral edema , cotransporter , pharmacology , western blot , chemistry , anesthesia , endocrinology , central nervous system , sodium , biochemistry , organic chemistry , gene
Our previous studies provided evidence that ischemia induces cerebral edema in part by stimulating activity of a luminal blood brain barrier (BBB) Na‐K‐Cl cotransporter (NKCC), leading to increased secretion of Na, Cl and water from blood into brain through functional coupling of NKCC with abluminal Na/K pump and Cl channels. K channels support NaCl transport across other epithelia by maintaining membrane potential, allowing continued Cl efflux via Cl channels. However, little is known about BBB K channels. In the present study we have identified the presence of the calcium‐activated KCa3.1 channel on cultured bovine cerebral microvascular endothelial cells (CMEC) by patch‐clamp, Western blot and immunocytochemical staining methods. Using radioisotopic flux methods and the KCa3.1‐specific blocker TRAM‐34, we also found a dose‐dependent TRAM‐34 inhibition of K+ flux in the CMEC. Further, we found that the CMEC TRAM‐34‐sensitive K+ flux was stimulated by oxygen‐glucose deprivation. Finally, in magnetic resonance (MR) Na spectroscopy and MR imaging in vivo studies we found that middle cerebral artery occlusion‐induced rat brain Na uptake and edema were significantly attenuated by TRAM‐34 (40 mg/kg IP). Our findings suggest that KCa3.1 blockade constitutes an attractive approach for reducing cerebral edema formation in the early stages of ischemic stroke or during brain surgery. Supported by AHA & NIH