| First Author | Laigle C | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 12 | Pages | e53266 |
| PubMed ID | 23285272 | Mgi Jnum | J:195740 |
| Mgi Id | MGI:5485124 | Doi | 10.1371/journal.pone.0053266 |
| Citation | Laigle C, et al. (2012) Deletion of TRAAK potassium channel affects brain metabolism and protects against ischemia. PLoS One 7(12):e53266 |
| abstractText | 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. |
