Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.
Division of Cardiology, Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, 19102, USA.
Sci Rep. 2018 May 2;8(1):6910. doi: 10.1038/s41598-018-25195-0.
Ion channels maintain numerous physiological functions and regulate signaling pathways. They are the key targets for cellular reactive oxygen species (ROS), acting as signaling switches between ROS and ionic homeostasis. We have carried out a paraquat (PQ) screen in Drosophila to identify ion channels regulating the ROS handling and survival in Drosophila melanogaster. Our screen has revealed that α1-subunits (D-type, T-type, and cacophony) of voltage-gated calcium channels (VGCCs) handle PQ-mediated ROS stress differentially in a gender-based manner. Since ROS are also involved in determining the lifespan, we discovered that the absence of T-type and cacophony decreased the lifespan while the absence of D-type maintained a similar lifespan to that of the wild-type strain. VGCCs are also responsible for electrical signaling in cardiac cells. The cardiac function of each mutant was evaluated through optical coherence tomography (OCT), which revealed that α1-subunits of VGCCs are essential in maintaining cardiac rhythmicity and cardiac function in an age-dependent manner. Our results establish specific roles of α1-subunits of VGCCs in the functioning of the aging heart.
离子通道维持着众多生理功能，并调节信号通路。它们是细胞活性氧（ROS）的关键靶点，在 ROS 和离子稳态之间充当信号开关。我们在果蝇中进行了百草枯（PQ）筛选，以鉴定调节 ROS 处理和果蝇黑腹果蝇生存的离子通道。我们的筛选表明，电压门控钙通道（VGCC）的α1 亚基（D 型、T 型和 cacophony）以性别为基础的方式差异调节 PQ 介导的 ROS 应激。由于 ROS 也参与决定寿命，我们发现 T 型和 cacophony 的缺失会降低寿命，而 D 型的缺失则保持与野生型菌株相似的寿命。VGCC 也负责心肌细胞的电信号传递。通过光学相干断层扫描（OCT）评估每个突变体的心脏功能，结果表明 VGCC 的α1 亚基在维持心脏节律性和心脏功能方面具有年龄依赖性的重要作用。我们的研究结果确立了 VGCC 的α1 亚基在衰老心脏功能中的特定作用。
