Dumanska Hanna, Telka Mariia, Veselovsky Nikolai
Department of Neuronal Network Physiology, Bogomoletz Institute of Physiology, National Academy of Science of Ukraine, Kyiv, Ukraine.
Front Cell Neurosci. 2023 Jul 3;17:1202083. doi: 10.3389/fncel.2023.1202083. eCollection 2023.
Hypoxia is a common factor of numerous ocular diseases that lead to dysfunctions and loss of retinal ganglion cells (RGCs) with subsequent vision loss. High-voltage-activated calcium channels are the main source of calcium entry into neurons. Their activity plays a central role in different signaling processes in health and diseases, such as enzyme activation, gene transcription, synaptic transmission, or the onset of cell death. This study aims to establish and evaluate the initial effect of the early stage of acute hypoxia on somatic HVA calcium currents in cultured RGCs. HVA calcium currents were recorded in RGCs using the whole-cell patch-clamp technique in the voltage-clamp mode. The fast local superfusion was used for a brief (up to 270 s) application of the hypoxic solution (pO < 5 mmHg). The switch from normoxic to hypoxic solutions and vice versa was less than 1 s. The HVA calcium channel activity was inhibited by acute hypoxia in 79% of RGCs (30 of 38 RGCs) in a strong voltage-dependent manner. The level of inhibition was independent of the duration of hypoxia or repeated applications. The hypoxia-induced inhibition of calcium currents had a strong correlation with the duration of hypoxia and showed the transition from reversible to irreversible at 75 s of hypoxia and longer. The results obtained are the first demonstration of the phenomena of HVA calcium current inhibition by acute hypoxia in RGCs and provide a conceptual framework for further research.
缺氧是众多眼部疾病的常见因素，这些疾病会导致视网膜神经节细胞（RGCs）功能障碍和丧失，进而导致视力丧失。高电压激活钙通道是钙离子进入神经元的主要来源。它们的活性在健康和疾病的不同信号传导过程中起着核心作用，如酶激活、基因转录、突触传递或细胞死亡的发生。本研究旨在建立和评估急性缺氧早期对培养的RGCs体细胞高电压激活钙电流的初始影响。使用全细胞膜片钳技术在电压钳模式下记录RGCs中的高电压激活钙电流。快速局部灌流用于短暂（最长270秒）施加缺氧溶液（pO < 5 mmHg）。从常氧溶液切换到缺氧溶液以及反之的切换时间小于1秒。急性缺氧以强烈的电压依赖性方式抑制了79%的RGCs（38个RGCs中的30个）中的高电压激活钙通道活性。抑制水平与缺氧持续时间或重复应用无关。缺氧诱导的钙电流抑制与缺氧持续时间密切相关，并且在缺氧75秒及更长时间时显示出从可逆到不可逆的转变。所获得的结果首次证明了急性缺氧在RGCs中抑制高电压激活钙电流的现象，并为进一步研究提供了概念框架。
