Feedback control of the ATP-sensitive K(+) current by cytosolic Ca(2+) contributes to oscillations of the membrane potential in pancreatic beta-cells.
During glucose stimulation, pancreatic beta-cells display membrane potential oscillations that correspond to intermittent Ca(2+) influx, leading to oscillations of the cytosolic free calcium concentration ([Ca(2+)](c)) and insulin secretion. The role of ATP-sensitive K(+) (K(+)-ATP) channels in the control of these oscillations was investigated by measuring the K(+)-ATP current (I(KATP)) with the perforated mode of the patch-clamp technique. No oscillations of I(KATP) were observed when glucose-stimulated beta-cells were kept hyperpolarized, thus with low and stable [Ca(2+)](c). However, increasing [Ca(2+)](c) by Ca(2+) influx (depolarizing pulses) or Ca(2+) mobilization (acetylcholine) transiently augmented I(KATP). This effect was abolished by tolbutamide, attenuated by increasing the glucose concentration in the medium, and prevented by abrogation of the [Ca(2+)](c) rise, which demonstrates that the current is really I(KATP) and that its increase is Ca(2+)-dependent. Injection of a current of a similar amplitude to that of the Ca(2+)-induced increase in I(KATP) was sufficient to repolarize glucose-stimulated beta-cells. These results suggest that, in the absence of [Ca(2+)](c) oscillations, no metabolic oscillations affect I(KATP) in pancreatic beta-cells. In contrast, [Ca(2+)](c) oscillations evoke I(KATP) oscillations. This mechanism may constitute the feedback loop controlling the glucose-induced oscillating electrical activity in beta-cells.
Rolland
Jean-François
JF
Unité d'Endocrinologie et Métabolisme, University of Louvain, Brussels, Belgium.
Henquin
Jean-Claude
JC
Gilon
Patrick
P
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D004553:Electric Conductivity; D004558:Electric Stimulation; D004594:Electrophysiology; D005246:Feedback; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009991:Oscillometry; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000502:physiology*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D002118:Calcium