Saafir Talib, Leng Tiandong, Inoue Koichi, Xiong Zhi-Gang, MacLeish Peter
Department of Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, USA.
Physiol Rep. 2025 May;13(9):e70290. doi: 10.14814/phy2.70290.
Acid-sensing ion channels (ASICs) are proton-gated cation channels belonging to the epithelial Na + channel/degenerin superfamily. In the CNS, ASICs are involved in synaptic plasticity, learning/memory, and acidosis-mediated injury. Previous studies showed that ASICs are expressed in rodent retina where activation likely participates in the phototransduction process and retinal integrity. However, there have been no studies examining the expression of ASICs in primate retina. Using molecular biology and patch-clamp techniques, we explored the expression of ASICs in monkey retina and cultured monkey retinal cells, and the electrophysiological/pharmacological properties of ASICs in cultured amacrine/ganglion cells. RT-PCR detected the expression of ASIC1a, 2a, 3, and 4 in intact monkey retina and cultured retinal cells. Patch-clamp recordings showed transient ASIC currents with a pH 0.5 of 4.69. The currents were almost completely blocked by amiloride (100 μM) but were insensitive to PcTx-1 (20 nM). The currents were potentiated by zinc (100 μM) and showed recovery from desensitization with a time constant of 0.18 s and were resistant to low conditioning pH with a pH 0.5 for steady-state inactivation of 6.45. Our results for the first time demonstrate the expression of functional ASICs in primate amacrine/ganglion cells and suggest that ASIC currents in these cells are mediated predominantly by ASIC2a containing channels.
酸敏感离子通道（ASICs）是属于上皮钠离子通道/退化蛋白超家族的质子门控阳离子通道。在中枢神经系统中，ASICs参与突触可塑性、学习/记忆以及酸中毒介导的损伤。先前的研究表明，ASICs在啮齿动物视网膜中表达，其激活可能参与光转导过程和视网膜完整性。然而，尚无研究检测ASICs在灵长类动物视网膜中的表达。我们运用分子生物学和膜片钳技术，探究了ASICs在猴视网膜及培养的猴视网膜细胞中的表达，以及培养的无长突细胞/神经节细胞中ASICs的电生理/药理学特性。逆转录聚合酶链反应（RT-PCR）检测到完整猴视网膜和培养的视网膜细胞中ASIC1a、2a、3和4的表达。膜片钳记录显示，pH 0.5为4.69时存在短暂的ASIC电流。这些电流几乎完全被氨氯吡脒（100 μM）阻断，但对蜂毒明肽-1（20 nM）不敏感。这些电流被锌（100 μM）增强，脱敏恢复的时间常数为0.18秒，并且对低预处理pH具有抗性，稳态失活的pH 0.5为6.45。我们的结果首次证明了功能性ASICs在灵长类无长突细胞/神经节细胞中的表达，并表明这些细胞中的ASIC电流主要由含ASIC2a的通道介导。
