The neuroprotective impact of the leak potassium channel TASK1 on stroke development in mice
| Autor: | Guido Stoll, Christoph Kleinschnitz, Tilman Broicher, Sven G. Meuth, Douglas A. Bayliss, Heinz Wiendl, Madeleine Austinat, Stephan Fischer, Thomas Budde, Stefan Bittner, Stefan Braeuninger |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Potassium Channels Brain Ischemia Membrane Potentials Brain ischemia Receptor Cannabinoid CB2 Mice Receptor Cannabinoid CB1 Thalamus Medicine Hypoxia Brain Mice Knockout Neurons Brain Depolarization Infarction Middle Cerebral Artery Cerebral ischemia Two-pore domain potassium channels Potassium channel Stroke Neurology Anesthesia Cardiology Acidosis medicine.medical_specialty Polyunsaturated Alkamides Ischemia TRPV Cation Channels Nerve Tissue Proteins Arachidonic Acids In Vitro Techniques Neuroprotection Article lcsh:RC321-571 TASK channels TASK1−/− mice Slice preparation Potassium Channels Tandem Pore Domain Internal medicine Animals RNA Messenger Transient middle cerebral artery occlusion lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry business.industry medicine.disease Blockade Mice Inbred C57BL Electrophysiology Thalamic neurons business Endocannabinoids |
| Zdroj: | Neurobiology of Disease, Vol 33, Iss 1, Pp 1-11 (2009) |
| Popis: | Oxygen depletion (O(2)) and a decrease in pH are initial pathophysiological events in stroke development, but secondary mechanisms of ischemic cell death are incompletely understood. By patch-clamp recordings of brain slice preparations we show that TASK1 and TASK3 channels are inhibited by pH-reduction (42+/-2%) and O(2) deprivation (36+/-5%) leading to membrane depolarization, increased input resistance and a switch in action potential generation under ischemic conditions. In vivo TASK blockade by anandamide significantly increased infarct volumes at 24 h in mice undergoing 30 min of transient middle cerebral artery occlusion (tMCAO). Moreover, blockade of TASK channels accelerated stroke development. Supporting these findings TASK1(-/-) mice developed significantly larger infarct volumes after tMCAO accompanied by worse outcome in functional neurological tests compared to wild type mice. In conclusion, our data provide evidence for an important role of functional TASK channels in limiting tissue damage during cerebral ischemia. |
| Databáze: | OpenAIRE |
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