Modeling the Impact of Store-Operated Ca2+ Entry on Intracellular Ca2+ Oscillations

Math Biosci. 2006 Dec;204(2):232-49. doi: 10.1016/j.mbs.2006.03.001. Epub 2006 Apr 19.

Abstract

Calcium (Ca2+) oscillations play fundamental roles in various cell signaling processes and have been the subject of numerous modeling studies. Here we have implemented a general mathematical model to simulate the impact of store-operated Ca2+ entry on intracellular Ca2+ oscillations. In addition, we have compared two different models of the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and their influences on intracellular Ca2+ oscillations. Store-operated Ca2+ entry following Ca2+ depletion of endoplasmic reticulum (ER) is an important component of Ca2+ signaling. We have developed a phenomenological model of store-operated Ca2+ entry via store-operated Ca2+ (SOC) channels, which are activated upon ER Ca2+ depletion. The depletion evokes a bi-phasic Ca2+ signal, which is also produced in our mathematical model. The IP3R is an important regulator of intracellular Ca2+ signals. This IP3 sensitive Ca2+ channel is also regulated by Ca2+. We apply two IP3R models, the Mak-McBride-Foskett model and the De Young and Keizer model, with significantly different channel characteristics. Our results show that the two separate IP3R models evoke intracellular Ca2+ oscillations with different frequencies and amplitudes. Store-operated Ca2+ entry affects the oscillatory behavior of these intracellular Ca2+ oscillations. The IP3 threshold is altered when store-operated Ca2+ entry is excluded from the model. Frequencies and amplitudes of intracellular Ca2+ oscillations are also altered without store-operated Ca2+ entry. Under certain conditions, when intracellular Ca2+ oscillations are absent, excluding store-operated Ca2+ entry induces an oscillatory response. These findings increase knowledge concerning store-operated Ca2+ entry and its impact on intracellular Ca2+ oscillations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / physiology*
  • Calcium Signaling / physiology*
  • Calcium-Transporting ATPases / metabolism
  • Computer Simulation
  • Endoplasmic Reticulum / metabolism
  • Epithelial Cells / metabolism
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors / physiology
  • Kidney Tubules / metabolism
  • Kinetics
  • Models, Biological*
  • Rats

Substances

  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Inositol 1,4,5-Trisphosphate
  • Calcium-Transporting ATPases
  • Calcium