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阐明维持小鼠视杆细胞离子动态平衡所需的 ATP 消耗因子的组成。

Clarifying the composition of the ATP consumption factors required for maintaining ion homeostasis in mouse rod photoreceptors.

机构信息

Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Shiga, Japan.

出版信息

Sci Rep. 2023 Aug 29;13(1):14161. doi: 10.1038/s41598-023-40663-y.

Abstract

To date, no effective treatment has been established for photoreceptor loss due to energy imbalances, but numerous therapeutic approaches have reported some success in slowing photoreceptor degeneration by downregulating energy demand. However, the detailed mechanisms remain unclear. This study aimed to clarify the composition of ATP consumption factors in photoreceptors in darkness and in light. We introduced mathematical formulas for ionic current activities combined with a phototransduction model to form a new mathematical model for estimating the energy expenditure of each ionic current. The proposed model included various ionic currents identified in mouse rods using a gene expression database incorporating an available electrophysiological recording of each specific gene. ATP was mainly consumed by Na/K-ATPase and plasma membrane Ca-ATPase pumps to remove excess Na and Ca. The rod consumed 7 [Formula: see text] 10 molecules of ATP s, where 65% was used to remove ions from the cyclic nucleotide-gated channel and 20% from the hyperpolarization-activated current in darkness. Increased light intensity raised the energy requirements of the complex phototransduction cascade mechanisms. Nevertheless, the overall energy consumption was less than that in darkness due to the significant reduction in ATPase activities, where the hyperpolarization-activated current proportion increased to 83%. A better understanding of energy demand/supply may provide an effective tool for investigating retinal pathophysiological changes and analyzing novel therapeutic treatments related to the energy consumption of photoreceptors.

摘要

迄今为止,对于由于能量失衡导致的光感受器损失,还没有确立有效的治疗方法,但许多治疗方法通过下调能量需求报告了一些减缓光感受器变性的成功。然而,其详细的机制仍不清楚。本研究旨在阐明在黑暗中和在光下光感受器中 ATP 消耗因素的组成。我们引入了结合光转导模型的离子电流活动的数学公式,从而形成了一种新的数学模型,用于估计每个离子电流的能量消耗。所提出的模型包括使用整合了每个特定基因的可用电生理记录的基因表达数据库,在鼠杆中鉴定出的各种离子电流。ATP 主要被 Na/K-ATPase 和质膜 Ca-ATPase 泵消耗,以去除多余的 Na 和 Ca。在黑暗中,杆状细胞消耗 7 [Formula: see text] 10 个 ATP 分子,其中 65%用于从环核苷酸门控通道中去除离子,20%用于从超极化激活电流中去除离子。增加的光强度提高了复杂的光转导级联机制的能量需求。然而,由于 ATPase 活性的显著降低,整体能量消耗低于黑暗状态,其中超极化激活电流的比例增加到 83%。更好地了解能量的供需可能为研究视网膜病理生理变化以及分析与光感受器能量消耗相关的新型治疗方法提供有效的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f4a/10465610/07b9e772b787/41598_2023_40663_Fig1_HTML.jpg

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