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

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.