Differential Effects of Energy Deprivation on Intracellular Sodium Homeostasis in Neurons and Astrocytes
Differential Effects of Energy Deprivation on Intracellular Sodium Homeostasis in Neurons and Astrocytes
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DOI：
10.1002/jnr.23995
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发表时间：
2017-11-01
影响因子：
4.2
通讯作者：
Rose, Christine R.
中科院分区：
文献类型：
--
作者：
Gerkau, Niklas J.;Rakers, Cordula;Rose, Christine R.
通过Na+/K+-ATP酶（NKA）维持低的细胞内钠浓度对脑功能至关重要。在神经元和神经胶质细胞中，需要NKA活性来抵消由于电压门控和配体门控通道的开放和/或钠依赖性次级活性转运蛋白的激活而引起的钠梯度变化。由于NKA消耗约50%的细胞ATP，钠稳态严格依赖于完整的细胞能量代谢。尽管电信号的能量消耗很高，但神经元本身并不含有大量的能量储存，而是依赖于与周围星形胶质细胞的密切代谢相互作用。在局灶性缺血期间观察到的能量供应中断导致神经元和星形胶质细胞中ATP的快速下降。越来越多的证据表明，细胞内钠的失调是细胞ATP减少的固有后果，触发其他离子（特别是钾、钙和质子）的细胞外和细胞内稳态的继发性失效，从而促进兴奋性毒性。然而，神经元和星形胶质细胞之间有害钠内流的特征、细胞机制和直接后果不同。此外，最近的研究表明，完整的星形胶质细胞代谢和钠稳态对于维持周围神经元的钠稳态以及它们从强加的钠流入中恢复的能力是至关重要的。了解代谢失败时钠增加的机制以及神经元和神经胶质细胞的差异反应以及它们的代谢相互作用对于完全揭示能量耗尽后导致细胞功能障碍，失败和细胞死亡的事件至关重要。(C)2017年Wiley Periodicals，Inc.
The maintenance of a low intracellular sodium concentration by the Na+/K+-ATPase (NKA) is critical for brain function. In both neurons and glial cells, NKA activity is required to counteract changes in the sodium gradient due to opening of voltage-and ligand-gated channels and/or activation of sodium-dependent secondary active transporters. Because NKA consumes about 50% of cellular ATP, sodium homeostasis is strictly dependent on an intact cellular energy metabolism. Despite the high energetic costs of electrical signaling, neurons do not contain significant energy stores themselves, but rely on a closemetabolic interaction with surrounding astrocytes. A disruption of energy supply as observed during focal ischemia causes a rapid drop in ATP in both neurons and astrocytes. There is accumulating evidence that dysregulation of intracellular sodium is an inherent consequence of a reduction in cellular ATP, triggering secondary failure of extra-and intracellular homeostasis of other ions - in particular potassium, calcium, and protons-and thereby promoting excitotoxicity. The characteristics, cellular mechanisms and direct consequences of harmful sodium influx, however, differ between neurons and astrocytes. Moreover, recent work has shown that an intact astrocyte metabolism and sodium homeostasis are critical to maintain the sodium homeostasis of surrounding neurons as well as their capacity to recover from imposed sodium influx. Understanding the mechanisms of sodium increases upon metabolic failure and the differential responses of neurons and glial cells as well as their metabolic interactions will be critical to fully unravel the events causing cellular malfunction, failure and cell death following energy depletion. (C) 2017 Wiley Periodicals, Inc.