Department of Cellular Membranology, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomoletz Street, Kyiv 01024, Ukraine.
Curr Neuropharmacol. 2021;19(9):1570-1589. doi: 10.2174/1570159X19666210125151824.
Acid-sensing ion channels (ASICs) are Na+-permeable ion channels activated by protons and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation. At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4, ASIC5) are encoded by five genes (ASIC1-ASIC5). Functional ASICs assembled in the plasma membrane are homo- or heteromeric trimers. ASIC1a-containing trimers are of particular interest as, in addition to sodium ions, they also conduct calcium ions and thus can trigger or regulate multiple cellular processes. ASICs are widely but differentially expressed in the central and peripheral nervous systems. In the mammalian brain, a majority of neurons express at least one ASIC subunit. Several recent reviews have summarized findings of the role of ASICs in the peripheral nervous system, particularly in nociception and proprioception, and the structure-function relationship of ASICs. However, there is little coverage on recent findings regarding the role of ASICs in the brain. Here we review and discuss evidence regarding the roles of ASICs: (i) as postsynaptic receptors activated by protons coreleased with glutamate at glutamatergic synapses; (ii) as modulators of synaptic transmission at glutamatergic synapses and GABAergic synapses; (iii) in synaptic plasticity, memory and learning; (iv) in some pathologies such as epilepsy, mood disorders and Alzheimer's disease.
酸敏离子通道（ASICs）是一种质子激活的 Na+通透性离子通道，主要表达于神经系统中。ASICs 作为 pH 感受器，引起神经元兴奋。至少有 8 种不同的 ASIC 亚基（包括 ASIC1a、ASIC1b、ASIC2a、ASIC2b、ASIC3、ASIC4、ASIC5）由 5 个基因（ASIC1-ASIC5）编码。功能性 ASICs 组装在质膜上，形成同源或异源三聚体。ASIC1a 包含的三聚体特别有趣，因为除了钠离子，它们还可以传导钙离子，因此可以触发或调节多种细胞过程。ASICs 在中枢和外周神经系统中广泛表达，但存在差异。在哺乳动物大脑中，大多数神经元至少表达一种 ASIC 亚基。最近的几篇综述总结了 ASICs 在周围神经系统中的作用，特别是在伤害感受和本体感受中的作用，以及 ASICs 的结构-功能关系。然而，关于 ASICs 在大脑中的作用的最新发现报道很少。在这里，我们回顾和讨论了 ASICs 的作用证据：（i）作为谷氨酸能突触中与谷氨酸共释放的质子激活的突触后受体；（ii）作为谷氨酸能突触和 GABA 能突触中突触传递的调节剂；（iii）在突触可塑性、记忆和学习中的作用；（iv）在一些疾病中，如癫痫、情绪障碍和阿尔茨海默病。
