Modeling the dependence of the period of intracellular Ca2+ waves on SERCA expression

Biophys J. 2003 Sep;85(3):1474-81. doi: 10.1016/S0006-3495(03)74580-9.

Abstract

Contrary to intuitive expectations, overexpression of sarco-endoplasmic reticulum (ER) Ca(2+) ATPases (SERCAs) in Xenopus oocytes leads to a decrease in the period and an increase in the amplitude of intracellular Ca(2+) waves. Here we examine these experimental findings by modeling Ca(2+) release using a modified Othmer-Tang-model. An increase in the period and a reduction in the amplitude of Ca(2+) wave activity are obtained when increases in SERCA density are simulated while keeping all other parameters of the model constant. However, Ca(2+) wave period can be reduced and the wave amplitude and velocity can be significantly increased when an increase in the luminal ER Ca(2+) concentration due to SERCA overexpression is incorporated into the model. Increased luminal Ca(2+) occurs because increased SERCA activity lowers cytosolic Ca(2+), which is partially replenished by Ca(2+) influx across the plasma membrane. These simulations are supported by experimental data demonstrating higher luminal Ca(2+) levels, decreased periods, increased amplitude, and increased velocity of Ca(2+) waves in response to increased SERCA density.

MeSH terms

  • Animals
  • Biophysical Phenomena
  • Biophysics
  • Blotting, Western
  • Calcium / chemistry
  • Calcium / metabolism*
  • Calcium-Transporting ATPases / biosynthesis*
  • Calcium-Transporting ATPases / chemistry*
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum / metabolism
  • Kinetics
  • Microscopy, Confocal
  • Mitochondria / metabolism
  • Models, Statistical
  • Oocytes / metabolism
  • RNA, Messenger / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Time Factors
  • Xenopus

Substances

  • RNA, Messenger
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Calcium