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.
The Journal of Membrane Biology – Springer Journals
Published: Jan 8, 2013
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