Simulation of spike-burst generation and Ca(2+) oscillation in pancreatic beta-cells.
Based on the experimental evidence that Na(+)-Ca(2+) exchange participates in the regulation of intracellular Ca(2+) concentration in pancreatic beta-cells, we construct a mathematical model for the cyclic spike-bursts and oscillations of intracellular Ca(2+) concentration. In our model, an increase in ATP concentration by the stimulation of glucose metabolism leads to the closure of ATP-sensitive K(+) channels (K(ATP) channels) and gradual depolarization to the threshold of voltage-gated Ca(2+) channels. Spikes are generated by the alternate activation of voltage-gated Ca(2+) and K(+) channels, causing Ca(2+) entry. The accumulated Ca(2+) ions are extruded by Na(+)-Ca(2+) exchange and Ca(2+) active transport. An increase in Na(+) influx through Na(+)-Ca(2+) exchangers results in a rise in intracellular Na(+) concentration and the activation of Na(+)-K(+) active transport. The consumption of ATP during the process of Ca(2+) extrusion leads to the opening of K(ATP) channels and repolarization. The present model could reproduce the main experimental features of the spike-burst activity and Ca(2+) oscillations following changes in the extracellular glucose concentration. As the rate of ATP production increases, the spike-burst pattern changes from bursts with long silent phases to continuous spiking. Changes in the pattern of electrical activity produced by the alteration of extracellular Na(+) and K(+) concentrations and the addition of ouabain could be reproduced in the present model.
Miwa
Y
Y
Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan. miwa@pharm.kyoto-u.ac.jp.
Imai
Y
Y
D000200:Action Potentials / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D005110:Extracellular Space / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D010042:Ouabain; D012964:Sodium; D011188:Potassium; D002118:Calcium