ATP Regulates Sodium Channel Kinetics in Pancreatic Islet Beta Cells |
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Authors: | Na Zou Xiao Wu Yan-Yan Jin Meng-Zao He Xin-Xin Wang Li-Da Su Marjan Rupnik Zhen-Yong Wu Li Liang Ying Shen |
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Institution: | 1. Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, People’s Republic of China 2. The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China 3. Department of Pediatrics, Second Hospital of Jiaxing, Jiaxing, Zhejiang, 314000, People’s Republic of China 4. Institute of Physiology, Faculty of Medicine University of Maribor, Slom?kov trg 15, 2000, Maribor, Slovenia
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Abstract: | Pancreatic beta cells act as glucose sensors, in which intracellular ATP (ATP]i) are altered with glucose concentration change. The characterization of voltage-gated sodium channels under different ATP]i remains unclear. Here, we demonstrated that increasing ATP]i within a certain range of concentrations (2–8 mM) significantly enhanced the voltage-gated sodium channel currents, compared with 2 mM cytosolic ATP. This enhancement was attenuated by even high intracellular ATP (12 mM). Furthermore, elevated ATP modulated the sodium channel kinetics in a dose-dependent manner. Increased ATP]i shifted both the current–voltage curve and the voltage-dependent inactivation curve of sodium channel to the right. Finally, the sodium channel recovery from inactivation was significantly faster when the intracellular ATP level was increased, especially in 8 mM ATP]i, which is an attainable concentration by the high glucose stimulation. In summary, our data suggested that elevated cytosolic ATP enhanced the activity of Na+ channels, which may play essential roles in modulating β cell excitability and insulin release when blood glucose concentration increases. |
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