期刊
JOURNAL OF MEMBRANE BIOLOGY
卷 246, 期 2, 页码 101-107出版社
SPRINGER
DOI: 10.1007/s00232-012-9506-7
关键词
ATP; Beta cell; Excitability; Kinetics; Na+ channel; Pancreas
资金
- National Foundation of Natural Science of China [31070945, 81170733, 31100780, 30600168]
- National Foundation of Natural Science
- Research Grants Council of Hong Kong of China [30731160616]
- New Century Talent Award of the Ministry of Education of China [NCET-07-0751]
- Zhejiang Province Foundation of Natural Science [R206018]
- Foundation of Zhejiang Educational Committee [Y201121662]
- Chinese-Slovenian Scientific and Technological Cooperation [8-15]
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 beta cell excitability and insulin release when blood glucose concentration increases.
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