UNN Institute of Neuroscience, University of Nizhny Novgorod, Nizhny Novgorod, Russia.
UNN Institute of Neuroscience, University of Nizhny Novgorod, Nizhny Novgorod, Russia; UCL Institute of Neurology, London, UK.
Brain Res Bull. 2018 Jan;136:37-43. doi: 10.1016/j.brainresbull.2017.08.015. Epub 2017 Sep 7.
Astrocytes are involved in maintenance of synaptic microenvironment by glutamate uptake and K clearance. These processes are associated with net charge transfer across the membrane and therefore can be recorded as glutamate transporter (I) and K (I) currents. It has been previously shown that the blockade of I with BaCl enhances the I. Here we show that activity-dependent facilitation (5 stimuli at 50Hz) of I was not significantly different in BaCl compared to facilitation of I isolated by post-hoc subtraction of I. Nevertheless, BaCl abolished the activity-dependent prolongation of τ, which was observed for I isolated by post-hoc subtraction of I. This finding suggests that activity-dependent accumulation of extracellular K ([K]) causes astrocytic depolarization, which is responsible for the increase in τ of I The blockade of inward rectifying K channels (K) with BaCl makes astrocytic membrane potential insensitive to [K] elevation and thus abolishes this increase. Blockade of I with glutamate transporter blocker, DL-threo-β-benzyloxyaspartic acid (TBOA) did not significantly affect the amplitude of I but decreased its τ. However, activity dependent facilitations of both amplitude and τ of I were larger in TBOA, than in the control conditions. We suggest that activity-dependent accumulation of extracellular glutamate can enhance release of K. Thus activity-dependent changes in [K] can affect glutamate dwell-time in the synaptic cleft, and vice versa, extracellular glutamate accumulation can affect [K] time-course. Our finding is important for understanding of the astrocytic mechanisms in glutamate excitotoxicity and in diseases related to disruption of K homeostasis (e.g. stroke, migraine, and epilepsy).
星形胶质细胞通过摄取谷氨酸和清除 K+来维持突触微环境。这些过程与跨膜的净电荷转移有关，因此可以记录为谷氨酸转运体（I）和 K+（I）电流。先前已经表明，用 BaCl2 阻断 I 可以增强 I。在这里，我们表明，与通过事后减法分离的 I 相比，BaCl2 中 I 的活动依赖性易化（50Hz 时 5 个刺激）没有显着差异。然而，BaCl2 消除了通过事后减法分离的 I 观察到的 I 的活性依赖性延长 τ。这一发现表明，细胞外 K+（[K+]）的活性依赖性积累导致星形胶质细胞去极化，这是导致 I 的 τ 增加的原因。内向整流 K+通道（K+）的阻断用 BaCl2 使星形胶质细胞膜电位对 [K+]升高不敏感，从而消除了这种增加。用谷氨酸转运体阻滞剂 DL-threo-β-苯甲酰氧基天冬氨酸（TBOA）阻断 I 不会显着影响 I 的幅度，但会降低其 τ。然而，在 TBOA 中，I 的幅度和 τ 的活动依赖性易化作用均大于对照条件。我们认为，细胞外谷氨酸的活性依赖性积累可以增强 K+的释放。因此，[K+]的活性依赖性变化可以影响谷氨酸在突触裂隙中的停留时间，反之亦然，细胞外谷氨酸的积累可以影响 [K+]的时间过程。我们的发现对于理解谷氨酸兴奋性毒性和与 K+动态平衡破坏相关的疾病（例如中风、偏头痛和癫痫）中的星形胶质细胞机制非常重要。
