Astrocytes Restrict Discharge Duration and Neuronal Sodium Loads during Recurrent Network Activity-猫眼课题宝

DOI：

10.1002/glia.22793

发表时间：

2015-06-01

期刊：

GLIA

影响因子：

6.2

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Karus, Claudia;Mondragao, Miguel A.;Rose, Christine R.

钠离子流入活跃的神经元是一个非常耗能的过程，必须严格限制。星形胶质细胞可以在此发挥重要作用，因为它们从细胞外空间摄取谷氨酸和钾，从而抑制神经元兴奋。在这里，我们在小鼠海马脑片进行钠成像结合场电位和全细胞膜片钳记录和测量细胞外钾（[K +]（o））。无镁、含荷包牡丹碱的生理盐水诱导网络活动，在此期间神经元表现出反复发作的癫痫样爆发，伴随[K +]（o）和星形胶质细胞去极化的短暂增加。在爆发，神经元显示钠增加高达22毫米。星形胶质细胞钠浓度增加高达8.5毫米，这可能是其次低于基线。网络钠振荡依赖于动作电位和离子型谷氨酸受体的激活。谷氨酸摄取的抑制引起加速，随后是电活动的停止，不可逆的钠增加和神经元肿胀。神经胶质毒素NaFAc（氟乙酸钠）导致星形胶质细胞钠浓度升高，并通过Na +/K +-ATP酶减少神经胶质细胞对谷氨酸和钾的摄取。此外，NaFAc延长癫痫样发作，引起神经元钠的升高，并显着延长伴随的钠信号，最有可能是因为星形胶质细胞对谷氨酸和钾的清除率降低。我们的实验证实，反复出现的神经元爆发引起神经元和星形胶质细胞中的钠瞬变，并证实谷氨酸转运蛋白对网络活动的重要作用。他们认为星形胶质细胞限制放电持续时间，并表明完整的星形胶质细胞代谢对于神经元在同步活动期间从钠负荷恢复的能力至关重要。GLIA 2015; 63：936 - 957

Influx of sodium ions into active neurons is a highly energy-expensive process which must be strictly limited. Astrocytes could play an important role herein because they take up glutamate and potassium from the extracellular space, thereby dampening neuronal excitation. Here, we performed sodium imaging in mouse hippocampal slices combined with field potential and whole-cell patch-clamp recordings and measurement of extracellular potassium ([K+](o)). Network activity was induced by Mg2+-free, bicuculline-containing saline, during which neurons showed recurring epileptiform bursting, accompanied by transient increases in [K+](o) and astrocyte depolarizations. During bursts, neurons displayed sodium increases by up to 22 mM. Astrocyte sodium concentration increased by up to 8.5 mM, which could be followed by an undershoot below baseline. Network sodium oscillations were dependent on action potentials and activation of ionotropic glutamate receptors. Inhibition of glutamate uptake caused acceleration, followed by cessation of electrical activity, irreversible sodium increases, and swelling of neurons. The gliotoxin NaFAc (sodium-fluoroacetate) resulted in elevation of astrocyte sodium concentration and reduced glial uptake of glutamate and potassium uptake through Na+/K+-ATPase. Moreover, NaFAc extended epileptiform bursts, caused elevation of neuronal sodium, and dramatically prolonged accompanying sodium signals, most likely because of the decreased clearance of glutamate and potassium by astrocytes. Our experiments establish that recurrent neuronal bursting evokes sodium transients in neurons and astrocytes and confirm the essential role of glutamate transporters for network activity. They suggest that astrocytes restrict discharge duration and show that an intact astrocyte metabolism is critical for the neurons' capacity to recover from sodium loads during synchronized activity. GLIA 2015;63:936-957

Astrocytes Restrict Discharge Duration and Neuronal Sodium Loads during Recurrent Network Activity

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