Modeling of Ca2+ Flux in Pancreatic Beta-Cells: Role of the Plasma Membrane and Intracellular Stores

Am J Physiol Endocrinol Metab. 2003 Jul;285(1):E138-54. doi: 10.1152/ajpendo.00194.2002. Epub 2003 Mar 18.

Abstract

We have developed a detailed mathematical model of ionic flux in beta-cells that includes the most essential channels and pumps in the plasma membrane. This model is coupled to equations describing Ca2+, inositol 1,4,5-trisphosphate (IP3), ATP, and Na+ homeostasis, including the uptake and release of Ca2+ by the endoplasmic reticulum (ER). In our model, metabolically derived ATP activates inward Ca2+ flux by regulation of ATP-sensitive K+ channels and depolarization of the plasma membrane. Results from the simulations support the hypothesis that intracellular Na+ and Ca2+ in the ER can be the main variables driving both fast (2-7 osc/min) and slow intracellular Ca2+ concentration oscillations (0.3-0.9 osc/min) and that the effect of IP3 on Ca2+ leak from the ER contributes to the pattern of slow calcium oscillations. Simulations also show that filling the ER Ca2+ stores leads to faster electrical bursting and Ca2+ oscillations. Specific Ca2+ oscillations in isolated beta-cell lines can also be simulated.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Animals
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / metabolism
  • Cell Membrane / metabolism
  • Endoplasmic Reticulum / metabolism
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Intracellular Membranes / metabolism
  • Ion Channels / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Potassium Channels / metabolism
  • Reproducibility of Results
  • Sodium Channels / metabolism
  • Sodium-Calcium Exchanger / metabolism

Substances

  • Ion Channels
  • Potassium Channels
  • Sodium Channels
  • Sodium-Calcium Exchanger
  • Inositol 1,4,5-Trisphosphate
  • Calcium-Transporting ATPases
  • Calcium