Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart.
Drosophila Voltage-Gated Calcium Channel α1-Subunits Regulate Cardiac Function in the Aging Heart.
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DOI：
10.1038/s41598-018-25195-0
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发表时间：
2018-05-02
影响因子：
4.6
通讯作者：
Gururaja Rao S
中科院分区：
文献类型：
--
作者：
Lam A;Karekar P;Shah K;Hariharan G;Fleyshman M;Kaur H;Singh H;Gururaja Rao S
离子通道维持许多生理功能并调节信号传导途径。它们是细胞活性氧（ROS）的关键靶点，充当ROS和离子稳态之间的信号开关。我们在果蝇中进行了百草枯（PQ）筛选，以确定调节果蝇ROS处理和存活的离子通道。我们的筛选结果显示，电压门控钙通道（VGCC）的α1亚基（D型，T型和杂音）以基于性别的方式不同地处理PQ介导的ROS应激。由于ROS也参与决定寿命，我们发现T型和杂音的缺乏降低了寿命，而D型的缺乏保持了与野生型菌株相似的寿命。VGCC还负责心脏细胞中的电信号。通过光学相干断层扫描（OCT）评估每个突变体的心脏功能，结果显示VGCC的α1-亚基在维持心脏节律和心脏功能方面具有年龄依赖性。我们的研究结果确立了VGCC α1亚基在衰老心脏功能中的特定作用。
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.
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影响因子：
5.6
作者：
Campiglio M;Flucher BE
通讯作者：
Flucher BE
影响因子：
2.9
作者：
Glancy, Brian;Willis, Wayne T.;Balaban, Robert S.
通讯作者：
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影响因子：
3.4
作者：
Chen, Qing;Niu, Yujie;Liu, Rujun
通讯作者：
Liu, Rujun
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4.6
作者：
Jeong K;Lee S;Seo H;Oh Y;Jang D;Choe J;Kim D;Lee JH;Jones WD
通讯作者：
Jones WD
钙和ROS：相互互动。
影响因子：
11.4
作者：
Görlach A;Bertram K;Hudecova S;Krizanova O
通讯作者：
Krizanova O