Contribution of the endoplasmic reticulum to the glucose-induced [Ca(2+)](c) response in mouse pancreatic islets.
Thapsigargin (TG), a blocker of Ca(2+) uptake by the endoplasmic reticulum (ER), was used to evaluate the contribution of the organelle to the oscillations of cytosolic Ca(2+) concentration ([Ca(2+)](c)) induced by repetitive Ca(2+) influx in mouse pancreatic beta-cells. Because TG depolarized the plasma membrane in the presence of glucose alone, extracellular K(+) was alternated between 10 and 30 mM in the presence of diazoxide to impose membrane potential (MP) oscillations. In control islets, pulses of K(+), mimicking regular MP oscillations elicited by 10 mM glucose, induced [Ca(2+)](c) oscillations whose nadir remained higher than basal [Ca(2+)](c). Increasing the depolarization phase of the pulses while keeping their frequency constant (to mimic the effects of a further rise of the glucose concentration on MP) caused an upward shift of the nadir of [Ca(2+)](c) oscillations that was reproduced by raising extracellular Ca(2+) (to increase Ca(2+) influx) without changing the pulse protocol. In TG-pretreated islets, the imposed [Ca(2+)](c) oscillations were of much larger amplitude than in control islets and occurred on basal levels. During intermittent trains of depolarizations, control islets displayed mixed [Ca(2+)](c) oscillations characterized by a summation of fast oscillations on top of slow ones, whereas no progressive summation of the fast oscillations was observed in TG-pretreated islets. In conclusion, the buffering capacity of the ER in pancreatic beta-cells limits the amplitude of [Ca(2+)](c) oscillations and may explain how the nadir between oscillations remains above baseline during regular oscillations or gradually increases during mixed [Ca(2+)](c) oscillations, two types of response observed during glucose stimulation.
Arredouani
Abdelilah
A
Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, UCL 55.30, B-1200 Brussels, Belgium.
Henquin
Jean-Claude
JC
Gilon
Patrick
P
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D027682:Cation Transport Proteins; D003981:Diazoxide / Q000494:pharmacology; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D011188:Potassium / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019284:Thapsigargin; D000251:Adenosine Triphosphatases; C022761:potassium transporting ATPase; D005947:Glucose; D003981:Diazoxide; D011188:Potassium