The two-pore domain K+ channel TASK-1 is closely associated with brain barriers and meninges.
Impairment of the blood-brain barrier (BBB), the blood-cerebrospinal fluid (CSF) barrier and brain-CSF barrier has been implicated in neuropathology of several brain disorders, such as amyotrophic lateral sclerosis, cerebral edema, multiple sclerosis, neural inflammation, ischemia and stroke. Two-pore domain weakly inward rectifying K+ channel (TWIK)-related acid-sensitive potassium (TASK)-1 channels (K2p3.1; KCNK3) are among the targets that contribute to the development of these pathologies. For example TASK-1 activity is inhibited by acidification, ischemia, hypoxia and several signaling molecules released under pathologic conditions. We have used immuno-histochemistry to examine the distribution of the TASK-1 protein in structures associated with the BBB, blood-CSF barrier, brain-CSF barrier, and in the meninges of adult rat. Dense TASK-1 immuno-reactivity (TASK-1-IR) was observed in ependymal cells lining the fourth ventricle at the brain-CSF interface, in glial cells that ensheath the walls of blood vessels at the glio-vascular interface, and in the meninges. In these structures, TASK-1-IR often co-localized with glial fibrillary associated protein (GFAP) or vimentin. This study provides anatomical evidence for localization of TASK-1 K+ channels in cells that segregate distinct fluid compartments within and surrounding the brain. We suggest that TASK-1 channels, in coordination with other ion channels (e.g., aquaporins and chloride channels) and transporters (e.g., Na+-K+-ATPase and Na+-K+-2Cl⁻ and by virtue of its heterogeneous distribution, may differentially contribute to the varying levels of K+ vital for cellular function in these compartments. Our findings are likely to be relevant to recently reported roles of TASK-1 in cerebral ischemia, stroke and inflammatory brain disorders.
Kanjhan
Refik
R
School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072, Australia. r.kanjhan@uq.edu.au
Pow
David V
DV
Noakes
Peter G
PG
Bellingham
Mark C
MC
D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D007150:Immunohistochemistry; D008578:Meninges / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014746:Vimentin / Q000378:metabolism
D020346:Aquaporins; D018118:Chloride Channels; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D014746:Vimentin; C420132:potassium channel subfamily K member 3; D011188:Potassium