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.

SUBMITTER: Laigle C 

PROVIDER: S-EPMC3532408 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature