Lions Eye Institute, Nedlands, Western Australia, 6009, Australia.
Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt.
Pflugers Arch. 2021 Sep;473(9):1455-1468. doi: 10.1007/s00424-021-02595-2. Epub 2021 Jul 13.
Light activation of the classical light-sensing retinal neurons, the photoreceptors, results in a graded change in membrane potential that ultimately leads to a reduction in neurotransmitter release to the post-synaptic retinal neurons. Photoreceptors show striking powers of adaptation, and for visual processing to function optimally, they must adjust their gain to remain responsive to different levels of ambient light intensity. The presence of a tightly controlled balance of inward and outward currents modulated by several different types of ion channels is what gives photoreceptors their remarkably dynamic operating range. Part of the resetting and modulation of this operating range is controlled by potassium and calcium voltage-gated channels, which are involved in setting the dark resting potential and synapse signal processing, respectively. Their essential contribution to visual processing is further confirmed in patients suffering from cone dystrophy with supernormal rod response (CDSRR) and congenital stationary night blindness type 2 (CSNB2), both conditions that lead to irreversible vision loss. This review will discuss these two types of voltage-gated ion channels present in photoreceptors, focussing on their structure and physiology, and their role in visual processing. It will also discuss the use and benefits of knockout mouse models to further study the function of these channels and what routes to potential treatments could be applied for CDSRR and CSNB2.
光激活经典的光感视网膜神经元,即光感受器,会导致膜电位的分级变化,最终导致神经递质释放到突触后的视网膜神经元减少。光感受器表现出惊人的适应能力,为了使视觉处理能够最佳地发挥作用,它们必须调整其增益,以保持对不同水平环境光强度的响应。内向和外向电流的平衡受到几种不同类型的离子通道的调节,这使得光感受器具有非常动态的工作范围。这种工作范围的重置和调节部分是由钾和钙电压门控通道控制的,它们分别参与设定暗休止电位和突触信号处理。在患有超正常棒状反应的 cone 营养不良症(CDSRR)和先天性静止性夜盲症 2 型(CSNB2)的患者中,它们对视觉处理的重要贡献得到了进一步证实,这两种情况都会导致不可逆转的视力丧失。这篇综述将讨论存在于光感受器中的这两种类型的电压门控离子通道,重点介绍它们的结构和生理学,以及它们在视觉处理中的作用。它还将讨论敲除小鼠模型的应用和益处,以进一步研究这些通道的功能,以及可以为 CDSRR 和 CSNB2 应用哪些潜在的治疗途径。