Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg 194223, Russia.
Int J Mol Sci. 2023 Aug 19;24(16):12974. doi: 10.3390/ijms241612974.
Proton-gated channels of the ASIC family are widely distributed in central neurons, suggesting their role in common neurophysiological functions. They are involved in glutamatergic neurotransmission and synaptic plasticity; however, the exact function of these channels remains unclear. One problem is that acidification of the synaptic cleft due to the acidic content of synaptic vesicles has opposite effects on ionotropic glutamate receptors and ASICs. Thus, the pH values required to activate ASICs strongly inhibit AMPA receptors and almost completely inhibit NMDA receptors. This, in turn, suggests that ASICs can provide compensation for post-synaptic responses in the case of significant acidifications. We tested this hypothesis by patch-clamp recordings of rat brain neuron responses to acidifications and glutamate receptor agonists at different pH values. Hippocampal pyramidal neurons have much lower ASICs than glutamate receptor responses, whereas striatal interneurons show the opposite ratio. Cortical pyramidal neurons and hippocampal interneurons show similar amplitudes in their responses to acidification and glutamate. Consequently, the total response to glutamate agonists at different pH levels remains rather stable up to pH 6.2. Besides these pH effects, the relationship between the responses mediated by glutamate receptors and ASICs depends on the presence of Mg and the membrane voltage. Together, these factors create a complex picture that provides a framework for understanding the role of ASICs in synaptic transmission and synaptic plasticity.
ASIC 家族的质子门通道广泛分布于中枢神经元中，表明它们在常见的神经生理功能中发挥作用。它们参与谷氨酸能神经传递和突触可塑性；然而，这些通道的确切功能仍不清楚。一个问题是，由于突触小泡的酸性内容，突触间隙的酸化对离子型谷氨酸受体和 ASIC 产生相反的影响。因此，激活 ASIC 所需的 pH 值强烈抑制 AMPA 受体，并几乎完全抑制 NMDA 受体。反过来，这表明在发生显著酸化的情况下，ASIC 可以为突触后反应提供补偿。我们通过在不同 pH 值下对大鼠脑神经元对酸化和谷氨酸受体激动剂的反应进行膜片钳记录来测试这一假说。海马锥体神经元的 ASIC 比谷氨酸受体反应的幅度要低得多，而纹状体中间神经元则相反。皮质锥体神经元和海马中间神经元对酸化和谷氨酸的反应幅度相似。因此，在 pH 6.2 之前，不同 pH 值下谷氨酸受体激动剂的总反应仍然相当稳定。除了这些 pH 效应之外，由谷氨酸受体和 ASIC 介导的反应之间的关系取决于 Mg 的存在和膜电压。这些因素共同构成了一幅复杂的图景，为理解 ASIC 在突触传递和突触可塑性中的作用提供了一个框架。
