Down-regulation of Na plus -coupled glutamate transporter EAAT3 and EAAT4 by AMP-activated protein kinase

作者：Sopjani Mentor; Alesutan Ioana; Dermaku Sopjani Miribane; Fraser Scott; Kemp Bruce E; Foeller Michael; Lang Florian^*

来源：Journal of Neurochemistry, 2010, 113(6): 1426-1435.

DOI：10.1111/j.1471-4159.2010.06678.x

• AMPK
• brain
• energy depletion
• excitotoxicity
• hypoxia

P>The glutamate transporters EAAT3 and EAAT4 are expressed in neurons. They contribute to the cellular uptake of glutamate and aspartate and thus to the clearance of the excitatory transmitters from the extracellular space. During ischemia, extracellular accumulation of glutamate may trigger excitotoxicity. Energy depletion leads to activation of the AMP-activated protein kinase (AMPK), a kinase enhancing energy production and limiting energy expenditure. The present study thus explored the possibility that AMPK regulates EAAT3 and/or EAAT4. To this end, EAAT3 or EAAT4 were expressed in Xenopus oocytes with or without AMPK and electrogenic glutamate transport determined by dual electrode voltage clamp. In EAAT3- and in EAAT4-expressing oocytes glutamate generated a current (I(g)), which was half maximal (K(M)) at 74 mu M (EAAT3) or at 4 mu M (EAAT4) glutamate. Co-expression of constitutively active gamma R70QAMPK or of wild type AMPK did not affect K(M) but significantly decreased the maximal I(g) in both EAAT3- (by 34%) and EAAT4- (by 49%) expressing oocytes. Co-expression of the inactive mutant alpha K45RAMPK [alpha 1(K45R)beta 1 gamma 1] did not appreciably affect I(g). According to confocal microscopy and chemiluminescence co-expression of gamma R70QAMPK or of wild type AMPK reduced the membrane abundance of EAAT3 and EAAT4. The observations show that AMPK down-regulates Na+-coupled glutamate transport.

• 出版日期2010-6
• 单位河北医科大学