Voltage-dependent metabolic regulation of Kv2.1 channels in pancreatic beta-cells.
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.
Yoshida
Masashi
M
First Department of Comprehensive Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, Omiya 1-847, Saitama 330-8503, Japan.
Nakata
Masanori
M
Yamato
Shiho
S
Dezaki
Katsuya
K
Sugawara
Hitoshi
H
Ishikawa
San-e
SE
Kawakami
Masanobu
M
Yada
Toshihiko
T
Kakei
Masafumi
M
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D051669:Shab Potassium Channels / Q000378:metabolism*
D007328:Insulin; C496991:Kcnb1 protein, rat; D051669:Shab Potassium Channels; D000255:Adenosine Triphosphate; D005947:Glucose