title: Expression of the kcnk3 potassium channel gene lessens the injury from cerebral ischemia, most likely by a general influence on blood pressure.
abstract: We examined the possible protective effect of TASK-1 (TWIK-related acid-sensitive potassium channel-1, kcnk3) and -3 potassium channels during stroke. TASK-1 and TASK-3, members of the two pore domain (K2P or kcnk) potassium channel family, form hetero or homodimers and help set the resting membrane potential. We used male TASK-1 and TASK-3 knockout mice in a model of focal cerebral ischemia, permanent middle cerebral artery occlusion (pMCAO). Infarct volume was measured 48 h after pMCAO. The TASK-1 knockout brains had larger infarct volumes (P=0.004), and those in TASK-3 knockouts were unchanged. As the TASK-1 gene is expressed in adrenal gland, heart and possibly blood vessels, the higher infarct volumes in the TASK-1 knockout mice could be due to TASK-1 regulating blood vessel tone and hence blood pressure or influencing blood vessel microarchitecture and blood flow rate. Indeed, we found that male TASK-1 knockout mice had reduced blood pressure, likely explaining the increased brain injury seen after pMCAO. Thus to make precise conclusions about how TASK-1 protects neurons, neural- or organ-specific deletions of the gene will be needed. Nevertheless, a consequence of having TASK-1 channels expressed (in various non-neuronal tissues and organs) is that neuronal damage is lessened when stroke occurs.
authors.affiliation: Department of Pharmacology, University of Heidelberg, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Muhammad
authors.forename: M I
authors.initials: MI
authors.lastname: Aller
authors.forename: C
authors.initials: C
authors.lastname: Maser-Gluth
authors.forename: M
authors.initials: M
authors.lastname: Schwaninger
authors.forename: W
authors.initials: W
authors.lastname: Wisden
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D001808:Blood Vessels / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics* / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C511784:TASK3 protein, mouse; C420132:potassium channel subfamily K member 3