Deletion of TRAAK potassium channel affects brain metabolism and protects against ischemia

• Published in: PloS one 2012-12, Vol.7 (12), p.e53266
• Main Authors: Laigle, Christophe, Confort-Gouny, Sylviane, Le Fur, Yann, Cozzone, Patrick J, Viola, Angèle
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Bioengineering; Biology; Brain; Brain - diagnostic imaging; Brain - metabolism; Brain damage; Brain research; Cell death; Channels; Clonal deletion; Cloning; Cytoprotection - genetics; Edema; Energy Metabolism - genetics; Fatty acids; Female; Gene Deletion; Hypoxia-Ischemia, Brain - complications; Hypoxia-Ischemia, Brain - diagnostic imaging; Hypoxia-Ischemia, Brain - genetics; Hypoxia-Ischemia, Brain - prevention & control; Imaging; In vivo methods and tests; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - diagnostic imaging; Infarction, Middle Cerebral Artery - genetics; Infarction, Middle Cerebral Artery - metabolism; Inositol; Ischemia; Life Sciences; Magnetic resonance; Magnetic resonance imaging; Magnetic resonance spectroscopy; Male; Males; Medicine; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; Nervous system; Neurobiology; Neuroimaging; Neurons and Cognition; NMR; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; pH effects; Pharmacology; Physiological aspects; Physiological effects; Physiology; Potassium; Potassium channels; Potassium Channels - genetics; Radiography; Resonance; Rodents; Spectroscopy; Stem cells; Stroke; Taurine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0053266

Cerebral stroke is a worldwide leading cause of disability. The two-pore domain K⁺ channels identified as background channels are involved in many functions in brain under physiological and pathological conditions. We addressed the hypothesis that TRAAK, a mechano-gated and lipid-sensitive two-pore domain K⁺ channel, is involved in the pathophysiology of brain ischemia. We studied the effects of TRAAK deletion on brain morphology and metabolism under physiological conditions, and during temporary focal cerebral ischemia in Traak⁻/⁻ mice using a combination of in vivo magnetic resonance imaging (MRI) techniques and multinuclear magnetic resonance spectroscopy (MRS) methods. We provide the first in vivo evidence establishing a link between TRAAK and neurometabolism. Under physiological conditions, Traak⁻/⁻ mice showed a particular metabolic phenotype characterized by higher levels of taurine and myo-inositol than Traak⁺/⁺ mice. Upon ischemia, Traak⁻/⁻ mice had a smaller infarcted volume, with lower contribution of cellular edema than Traak⁺/⁺ mice. Moreover, brain microcirculation was less damaged, and brain metabolism and pH were preserved. Our results show that expression of TRAAK strongly influences tissue levels of organic osmolytes. Traak⁻/⁻ mice resilience to cellular edema under ischemia appears related to their physiologically high levels of myo-inositol and of taurine, an aminoacid involved in the modulation of mitochondrial activity and cell death. The beneficial effects of TRAAK deletion designate this channel as a promising pharmacological target for the treatment against stroke.