Involvement of TREK-1 activity in astrocyte function and neuroprotection under simulated ischemia conditions.
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.
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Xiao
X
Wu
Yang
Y
Liu
Xiaojing
X
Chen
Qian
Q
Sun
Ronghua
R
Tang
Wei
W
Wang
Zhiyuan
Z
Yu
Minjie
M
Xie
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002045:Bupivacaine / Q000494:pharmacology; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D016895:Culture Media, Serum-Free; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism; D006706:Homeostasis; D007511:Ischemia / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D024683:Potassium Channels, Tandem Pore Domain / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism
D016895:Culture Media, Serum-Free; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C103742:potassium channel protein TREK-1; D018698:Glutamic Acid; D011803:Quinine; D002045:Bupivacaine