Voltage-dependent metabolic regulation of Kv2.1 channels in pancreatic beta-cells

作者：Yoshida Masashi; Nakata Masanori; Yamato Shiho; Dezaki Katsuya; Sugawara Hitoshi; Ishikawa San E; Kawakami Masanobu; Yada Toshihiko; Kakei Masafumi^*

来源：Biochemical and Biophysical Research Communications, 2010, 396(2): 304-309.

DOI：10.1016/j.bbrc.2010.04.088

• Glucose metabolism
• Insulin secretion
• Kv channel
• Phosphorylation

Voltage-gated potassium channels (Kv channels) play a crucial role in formation of action potentials in response to glucose stimulation in pancreatic beta-ells. We previously reported that the Kv channel is regulated by glucose metabolism, particularly by MgATP. We examined whether the regulation of Kv channels is voltage-dependent and mechanistically related with phosphorylation of the channels. In rat pancreatic beta-cells, suppression of glucose metabolism with low glucose concentrations of 2.8 mM or less or by metabolic inhibitors decreased the Kv2.1-channel activity at positive membrane potentials, while increased it at potentials negative to -10 mV, suggesting that modulation of Kv channels by glucose metabolism is voltage-dependent. Similarly, in HEK293 cells expressing the recombinant Kv2.1 channels, 0 mM but not 10 mM MgATP modulated the channel activity in a manner similar to that in beta-cells. Both steady-state activation and inactivation kinetics of the channel were shifted toward the negative potential in association with the voltage-dependent modulation of the channels by cytosolic dialysis of alkaline phosphatase in beta-cells. The modulation of Kv-channel current-voltage relations were also observed during and after glucose-stimulated electrical excitation. These results suggest that the cellular metabolism including MgATP production and/or channel phosphorylation/dephosphorylation underlie the physiological modulation of Kv2.1 channels during glucose-induced insulin secretion.

• 出版日期2010-5-28