Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase.
Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase.
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DOI：
10.1016/j.neuron.2012.08.032
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发表时间：
2012-09-20
期刊：
影响因子：
16.2
通讯作者：
MacVicar BA
中科院分区：
文献类型：
--
作者：
Choi HB;Gordon GR;Zhou N;Tai C;Rungta RL;Martinez J;Milner TA;Ryu JK;McLarnon JG;Tresguerres M;Levin LR;Buck J;MacVicar BA
星形胶质细胞被认为通过从其糖原储存和糖酵解向神经元提供底物来参与脑能量代谢。然而，参与代谢传感的分子以及负责大脑中不同细胞类型之间代谢耦合的分子途径尚未完全了解。在这里，我们展示了最近克隆的碳酸氢盐 (HCO3−) 传感器，即可溶性腺苷酸环化酶 (sAC)，在星形胶质细胞中高度表达，并通过生电 NaHCO3 协同转运蛋白 (NBC) 响应 HCO3− 进入而被激活。激活的 sAC 增加细胞内 cAMP 水平，导致糖原分解、糖酵解增强，并将乳酸释放到细胞外空间，随后被神经元吸收用作能量底物。这一过程在 [K+]ext 的广泛生理范围内以及在血糖发作期间被招募，有助于维持突触功能。这些数据揭示了星形胶质细胞中负责大脑代谢与神经元耦合的分子途径。
Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO3−) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO3− entry via the electrogenic NaHCO3 cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K+]ext and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons.
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DOI：
10.1073/pnas.0400050101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Esposito, G;Jaiswal, BS;Gossen, JA
通讯作者：
Gossen, JA
影响因子：
56.9
作者：
Alle, Henrik;Roth, Arnd;Geiger, Joerg R. P.
通讯作者：
Geiger, Joerg R. P.
影响因子：
6.2
作者：
BOYARSKY, G;RANSOM, B;BORON, WF
通讯作者：
BORON, WF
影响因子：
6.2
作者：
DRINGEN, R;HAMPRECHT, B
通讯作者：
HAMPRECHT, B
影响因子：
4.8
作者：
Hallows, Kenneth R.;Wang, Huamin;Pastor-Soler, Nuria M.
通讯作者：
Pastor-Soler, Nuria M.