Aquaporin-4 deficiency down-regulates glutamate uptake and GLT-1 expression in astrocytes.
The role of aquaporin-4 in water transport has been extensively investigated, while little information exists regarding its contribution to astrocytic functions such as the action to glutamatergic transmission. Since aquaporin-4 has been detected widely co-localized with glutamate transporter 1 (GLT-1) and glutamate transporters also present water transport properties, we investigated the regulative role of aquporin-4 on glutamate transporter using primary cultured astrocytes from aquaporin-4 knockout (AQP4(-/-)) mice. It was demonstrated that lack of aquaporin-4 down-regulated astrocytic expression of GLT-1 but not of glutamate/aspartate transporter (GLAST). The result from [(3)H]D,L-glutamate uptake analysis showed a lower uptake capability in AQP4(-/-) astrocytes. Furthermore, MTT and LDH assays indicated less cellular toxicity induced by excessive glutamate in AQP4(-/-) genotype. These findings provide direct evidences for the first time that aquaporin-4 plays an important role in the function of glutamate transporters. And the present study will improve our understanding of aquaporin-4-glutamanergic biology.
Zeng
Xiao-Ning
XN
Laboratory of Neuropharmacology, Department of Anatomy, Histology and Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, PR China.
Sun
Xiu-Lan
XL
Gao
Lin
L
Fan
Yi
Y
Ding
Jian-Hua
JH
Hu
Gang
G
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity; D009435:Synaptic Transmission / Q000235:genetics
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D009498:Neurotoxins; D018698:Glutamic Acid