The two-pore domain K+ channel TASK-1 is closely associated with brain barriers and meninges

J Mol Histol. 2010 Dec;41(6):315-23. doi: 10.1007/s10735-010-9293-3. Epub 2010 Sep 11.

Abstract

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.

MeSH terms

  • Animals
  • Aquaporins / metabolism
  • Blood-Brain Barrier / metabolism*
  • Cerebrospinal Fluid / metabolism
  • Chloride Channels / metabolism
  • Homeostasis / physiology
  • Immunohistochemistry
  • Meninges / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Potassium / metabolism
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Rats
  • Rats, Wistar
  • Vimentin / metabolism

Substances

  • Aquaporins
  • Chloride Channels
  • Nerve Tissue Proteins
  • Potassium Channels, Tandem Pore Domain
  • Vimentin
  • potassium channel subfamily K member 3
  • Potassium