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Clarifying the composition of the ATP consumption factors required for maintaining ion homeostasis in mouse rod photoreceptors
Scientific Reports ( IF 3.8 ) Pub Date : 2023-08-29 , DOI: 10.1038/s41598-023-40663-y
Yuttamol Muangkram 1 , Yukiko Himeno 1 , Akira Amano 1
Affiliation  

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 Ca2+-ATPase pumps to remove excess Na+ and Ca2+. The rod consumed 7 \(\times\) 107 molecules of ATP s−1, 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.



中文翻译:

阐明维持小鼠视杆光感受器离子稳态所需的 ATP 消耗因子的组成

迄今为止,尚未建立有效的治疗方法来治疗由于能量不平衡导致的光感受器损失,但许多治疗方法已报道通过下调能量需求在减缓光感受器退化方面取得了一些成功。然而,详细机制仍不清楚。本研究旨在阐明黑暗和光照下光感受器中 ATP 消耗因子的组成。我们引入了离子电流活动的数学公式与光转导模型相结合,形成了一个新的数学模型来估计每个离子电流的能量消耗。所提出的模型包括使用基因表达数据库在小鼠视杆中识别的各种离子电流,该数据库结合了每个特定基因的可用电生理记录。ATP主要被Na + /K + -ATP酶和质膜Ca 2+ -ATP酶泵消耗以去除过量的Na +和Ca 2+。该杆消耗了 7 \(\times\) 10 7 ATP s -1分子,其中 65% 用于从环核苷酸门控通道中去除离子,20% 用于在黑暗中从超极化激活电流中去除离子。光强度的增加提高了复杂光转导级联机制的能量需求。然而,由于ATP酶活性显着降低,总体能量消耗低于黑暗中,其中超极化激活电流比例增加至83%。更好地了解能量需求/供应可以为研究视网膜病理生理变化和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。

更新日期:2023-08-30
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