title: Na⁺-Ca²⁺ exchanger mediates ChR2-induced [Ca²⁺]i elevation in astrocytes.
abstract: Intracellular Ca(2+) elevation resulting from different Ca(2+) pathways may play different roles in astrocyte functions. Channelrhodopsin-2 (ChR2), a light-gated cation channel, has been used to selectively stimulate astrocytes by inducing intracellular Ca(2+) ([Ca(2+)]i) elevation, but the exact underlying mechanism is still unclear. We found that in the absence of extracellular Ca(2+), light stimulation failed to induce [Ca(2+)]i elevation in astrocytes expressed ChR2. Pharmacological experiments excluded the involvement of Ca(2+)-induced Ca(2+) release from intracellular stores. Further experiments demonstrated that the ChR2-induced [Ca(2+)]i elevation was mainly mediated by reversal of the Na(+)-Ca(2+) exchanger following Na(+) influx through ChR2 channels. Since intracellular Na(+) homeostasis plays important roles in astrocytes, including the modulation of [Ca(2+)]i, neurotransmitter uptake and cell metabolism, our results indicate that ChR2 is a good candidate which could be used for mimicking the intracellular Na(+) disturbance in astrocytes that occurs in various physiological and pathological processes including the uptake of neurotransmitters and ischemia, as well as the activities of various cation channels, ion exchangers, and pumps.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Danqing
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Keqing
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Lou
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address: duanshumin@zju.edu.cn.
authors.forename: Shumin
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address: haowang@zju.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D000075402:Channelrhodopsins; D051379:Mice; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D000075402:Channelrhodopsins; D019831:Sodium-Calcium Exchanger
keywords: Astrocytes; Calcium elevation; Channelrhodopsin-2; Na(+)–Ca(2+) exchanger