title: Deletion of TRAAK potassium channel affects brain metabolism and protects against ischemia.
abstract: 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.
authors.affiliation: Centre de Résonance Magnétique Biologique et Médicale-CRMBM, Joint Research Unit n°7339-UMR 7339, National Center for Scientific Research-CNRS, Aix-Marseille Université-AMU, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Laigle
authors.forename: Sylviane
authors.initials: S
authors.lastname: Confort-Gouny
authors.forename: Yann
authors.initials: Y
authors.lastname: Le Fur
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Cozzone
authors.forename: Angèle
authors.initials: A
authors.lastname: Viola
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D019610:Cytoprotection / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics* / Q000517:prevention & control; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015221:Potassium Channels / Q000235:genetics*; D011859:Radiography
chemical_list: C503433:Kcnk4 protein, mouse; D015221:Potassium Channels