Referenced in: none

Automatically associated channels: Kv2.1

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

Authors: Masashi Yoshida, Masanori Nakata, Shiho Yamato, Katsuya Dezaki, Hitoshi Sugawara, San-E Ishikawa, Masanobu Kawakami, Toshihiko Yada, Masafumi Kakei

Journal, date & volume: Biochem. Biophys. Res. Commun., 2010 May 28 , 396, 304-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20403337

Abstract
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 2.8mM 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, 0mM but not 10mM 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.