Dynamics of Fluids, Experimental Physics, Saarland University, 66123 Saarbrücken, Germany.
Department of Neurophysiology, Physiological Institute, University of Würzburg, 97070 Würzburg, Germany.
Cells. 2024 Nov 8;13(22):1852. doi: 10.3390/cells13221852.
Channelrhodopsins (ChRs) are light-gated ion channels originally discovered in algae and are commonly used in neuroscience for controlling the electrical activity of neurons with high precision. Initially-discovered ChRs were non-selective cation channels, allowing the flow of multiple ions, such as Na, K, H, and Ca, leading to membrane depolarization and triggering action potentials in neurons. As the field of optogenetics has evolved, ChRs with more specific ion selectivity were discovered or engineered, offering more precise optogenetic manipulation. This review highlights the natural occurrence and engineered variants of sodium-selective channelrhodopsins (NaChRs), emphasizing their importance in optogenetic applications. These tools offer enhanced specificity in Na ion conduction, reducing unwanted effects from other ions, and generating strong depolarizing currents. Some of the NaChRs showed nearly no desensitization upon light illumination. These characteristics make them particularly useful for experiments requiring robust depolarization or direct Na ion manipulation. The review further discusses the molecular structure of these channels, recent advances in their development, and potential applications, including a proposed drug delivery system using NaChR-expressing red blood cells that could be triggered to release therapeutic agents upon light activation. This review concludes with a forward-looking perspective on expanding the use of NaChRs in both basic research and clinical settings.
通道蛋白视紫红质（ChRs）最初在藻类中发现，是一种光门控离子通道，常用于神经科学领域，以高精度控制神经元的电活动。最初发现的 ChRs 是非选择性阳离子通道，允许多种离子（如 Na、K、H 和 Ca）流动，导致神经元去极化并引发动作电位。随着光遗传学领域的发展，发现或工程设计了具有更高离子选择性的 ChRs，提供了更精确的光遗传学操作。本综述重点介绍了具有钠选择性的通道蛋白视紫红质（NaChRs）的天然发生和工程变体，强调了它们在光遗传学应用中的重要性。这些工具在 Na 离子传导方面具有更高的特异性，减少了其他离子的不必要影响，并产生强烈的去极化电流。一些 NaChRs 在光照下几乎没有脱敏现象。这些特性使它们特别适用于需要强去极化或直接 Na 离子操作的实验。本综述进一步讨论了这些通道的分子结构、最近的发展进展以及潜在的应用，包括使用表达 NaChR 的红细胞作为药物输送系统的建议，该系统可以在光激活时触发释放治疗剂。本综述以对在基础研究和临床环境中扩展 NaChR 的使用的前瞻性展望结束。
