Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA.
Glia. 2022 Oct;70(10):1927-1937. doi: 10.1002/glia.24228. Epub 2022 Jun 9.
Volume transmission plays an essential role in CNS function, with neurotransmitters released from synapses diffusing through the extracellular space (ECS) to distant sites. Changes in the ECS volume fraction (α) will influence the diffusion and the concentration of transmitters within the ECS. We have recently shown that neuronal activity evoked by physiological photic stimuli results in rapid decreases in ECS α as large as 10% in the retina. We now characterize the cellular mechanisms responsible for this ECS shrinkage. We find that block of inwardly rectifying K channels with Ba , inhibition of the Na /K /2Cl cotransporter with bumetanide, or block of AQP4 water channels with TGN-020 do not diminish the light-evoked ECS decrease. Inhibition of the Na /HCO cotransporter by removing HCO from the superfusate, in contrast, reduces the light-evoked ECS decrease by 95.6%. Inhibition of the monocarboxylate transporter with alpha-cyano-4-hydroxycinnamate (4-CIN) also reduces the ECS shrinkage, but only by 32.5%. We tested whether the swelling of Müller cells, the principal glial cells of the retina, is responsible for the light-evoked ECS shrinkage. Light stimulation evoked a 6.3% increase in the volume of the fine processes of Müller cells. This volume increase was reduced by 97.1% when HCO was removed from the superfusate. We conclude that a large fraction of the activity-dependent decrease in ECS α is generated by the activation of the Na /HCO cotransporter in Müller cells. The monocarboxylate transporter may also contribute to the response.
容积传递在中枢神经系统功能中起着至关重要的作用，神经递质从突触释放后会扩散到细胞外间隙（extracellular space，ECS），到达远处的部位。细胞外间隙体积分数（α）的变化会影响递质在 ECS 中的扩散和浓度。我们最近发现，生理光刺激引起的神经元活动会导致视网膜中 ECSα 迅速减少 10%。现在我们对导致这种 ECS 收缩的细胞机制进行了特征描述。我们发现，用 Ba2+阻断内向整流钾通道、用布美他尼抑制钠/钾/2Cl 协同转运体或用 TGN-020 阻断水通道 AQP4，都不会减少光诱发的 ECS 减少。相比之下，从灌流液中去除 HCO3- 会抑制 Na/HCO3 协同转运体，使光诱发的 ECS 减少 95.6%。用 alpha-cyano-4-hydroxycinnamate（4-CIN）抑制单羧酸转运体也会减少 ECS 收缩，但仅减少 32.5%。我们测试了 Müller 细胞（视网膜的主要神经胶质细胞）的肿胀是否是光诱发 ECS 收缩的原因。光刺激引起 Müller 细胞的细突体积增加 6.3%。当从灌流液中去除 HCO3- 时，这种体积增加减少了 97.1%。我们得出结论，ECSα 的活性依赖性减少的很大一部分是由 Müller 细胞中 Na/HCO3 协同转运体的激活产生的。单羧酸转运体也可能对该反应有贡献。
