title: ATP regulates sodium channel kinetics in pancreatic islet beta cells.
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.
authors.affiliation: 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.
authors.forename: Na
authors.initials: N
authors.lastname: Zou
authors.forename: Xiao
authors.initials: X
authors.lastname: Wu
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Jin
authors.forename: Meng-Zao
authors.initials: MZ
authors.lastname: He
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Wang
authors.forename: Li-Da
authors.initials: LD
authors.lastname: Su
authors.forename: Marjan
authors.initials: M
authors.lastname: Rupnik
authors.forename: Zhen-Yong
authors.initials: ZY
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D010179:Pancreas / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D000255:Adenosine Triphosphate