Journal
NEURON
Volume 110, Issue 5, Pages 770-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2021.11.027
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Funding
- Beijing Municipal Science & Technology Commission [Z181100001318002, Z181100001518004]
- Beijing Nova Program [Z20111000680000]
- National Natural Science Foundation of China [31925017, 81821092, 92032000]
- National Key R&D Program of China [2020YFE0204000, 2019YFA0801603]
- Shenzhen-Hong Kong Institute of Brain Science [NYKFKT2019013]
- FENG Foundation
- Peking-Tsinghua Center for Life Sciences
- Boehringer Ingelheim-Peking University Postdoctoral Program
- National Center for Protein Sciences at Peking University
- State Key Laboratory of Membrane Biology at Peking University School of Life Sciences
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ATP, a key transmitter in the nervous system, is essential for normal physiological functions. Researchers have developed a highly sensitive ATP sensor, GRAB(ATP1.0), which enables real-time measurement of extracellular ATP release. This tool has been successfully used to monitor ATP dynamics in various experimental settings, providing valuable insights into its physiological and pathological roles.
The purinergic transmitter ATP (adenosine 5'-triphosphate) plays an essential role in both the central and peripheral nervous systems, and the ability to directly measure extracellular ATP in real time will increase our understanding of its physiological functions. Here, we developed a sensitive GPCR activation-based ATP sensor called GRAB(ATP1.0), with a robust fluorescence response to extracellular ATP when expressed in several cell types. This sensor has sub-second kinetics, has ATP affinity in the range of tens of nanomolar, and can be used to localize ATP release with subcellular resolution. Using this sensor, we monitored ATP release under a variety of in vitro and in vivo conditions, including stimuli-induced and spontaneous ATP release in primary hippocampal cultures, injury-induced ATP release in a zebrafish model, and lipopolysaccharides-induced ATP-release events in individual astrocytes in the mouse cortex. Thus, the GRAB(ATP1.0) sensor is a sensitive, versatile tool for monitoring ATP release and dynamics under both physiological and pathophysiological conditions.
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