Mécanismes de contrôle du potentiel de membrane de la cellule à insuline par le glucose et l'acétylcholine
(2003)
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- Authors
- Supervisors
- Gilon, Patrick
- Abstract
- During the feeding periods, the increase in glycemia is limited in time and amplitude by the hypoglycemic action of insulin that is secreted by pancreatic beta cells. These latter are electrically excitable and their membrane potential and electrical activity are primarily controlled by glucose. These effects have mainly been characterized in mouse islets in which, in the presence of a non-stimulating concentration of glucose (< or = to 6 mM), the membrane potential is at the resting level. When the glucose concentration increases (> or = to 7 mM), the acceleration of glucose metabolism inside the beta cell increases the ATP/ADP ratio, which closes the ATP-sensitive K+ channels (K+-ATP channels). This leads to depolarization of the plasma membrane and an oscillating electrical activity starts. Each oscillation of the membrane potential, usually referred to as a slow wave, consists of a depolarized phase on top of which a train of action potentials appears, and a repolarized phase without action potential. Glucose modulates the duration of the slow waves that become longer, with little change in their frequency, as its concentration increases (between 7 and 25 mM). When this concentration exceeds 25 mM, slow waves are transformed into a sustained depolarization with continuous spike activity. The changes in membrane potential are crucial for the control of beta cell function because each depolarization induces a concomitant rise in the cytosolic Ca2+ concentration ([Ca2+]c) which is the triggering signal for insulin secretion. Whereas it is unanimously admitted that the rise in the ATP/ADP ratio triggers the initial depolarization, via the closure of K+-ATP channels, the mechanisms driving the partial repolarization at the end of each slow wave has escaped identification. Among numerous hypothesis, it has been proposed that metabolic oscillations (intrinsic or dependent of [Ca2+]c) drive oscillation of the K+-ATP channels activity. To verify this hypothesis and evaluate the role of K+-ATP channels in the control of the partial repolarisation, we measured the K+-ATP current (IKATP) using the perforated configuration of the patch-clamp technique (voltage-clamp). No oscillations of IKATP were observed when glucose-stimulated beta cells were kept hyperpolarized, thus with low and stable [Ca2+]c. These results suggest that, in the absence of [Ca2+]c oscillations, no intrinsic metabolic oscillations affect IKATP in pancreatic beta cells. Conversely, increasing [Ca2+]c by Ca2+ influx (depolarizing pulses) or Ca2+ mobilization (acetylcholine) transiently augmented IKA
- Affiliations
Citations
Rolland, J.-F. (2003). Mécanismes de contrôle du potentiel de membrane de la cellule à insuline par le glucose et l’acétylcholine. https://hdl.handle.net/2078.5/110758