Abstract
Astrocytes play a fundamental role in the pathogenesis of ischemic neuronal death. The optimal operation of electrogenic astrocytic transporters and exchangers for some well-defined astrocyte brain homeostatic functions depends on the presence of K+ channels in the cell membranes and the hyperpolarized membrane potential. Our previous study showed that astrocytes functionally express two-pore domain K+ channel TREK-1, which helps to set the negative resting membrane potential. However, the roles of TREK-1 on astrocytic function under normal and ischemic conditions remain unclear. In this study, we investigated the expression of TREK-1 protein on cultured astrocytes and the effect of TREK-1 activity on astrocytic glutamate clearance capacity and release of s100β after simulated ischemic insult. TREK-1 immunoreactivity was up-regulated after hypoxia. Suppression of TREK-1 activity inhibited the glutamate clearance capability, enhanced the inflammatory secretion of astrocytes derived s100β and led to increased neuronal apoptosis after ischemic insult. Our results suggest that TREK-1 activity is involved in astrocytic function and neuronal survival. This would provide evidence showing astrocytic TREK-1 involvement in ischemia pathology which may serve as a potential therapeutic target in stroke.
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Acknowledgements
The investigation was supported by the National Natural Science Foundation of China (30971007, 81030021), Natural Science Foundation for outstanding young scholar of Hubei Province (2010CDA103) and National Basic Research Development Program (973 Program) of China (2011CB504403).
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Wu, X., Liu, Y., Chen, X. et al. Involvement of TREK-1 Activity in Astrocyte Function and Neuroprotection Under Simulated Ischemia Conditions. J Mol Neurosci 49, 499–506 (2013). https://doi.org/10.1007/s12031-012-9875-5
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DOI: https://doi.org/10.1007/s12031-012-9875-5