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

Contrary to intuitive expectations, overexpression of sarco-endoplasmic reticulum (ER) Ca2+ ATPases (SERCAs) in Xenopus oocytes leads to a decrease in the period and an increase in the amplitude of intracellular Ca2+ waves. Here we examine these experimental findings by modeling Ca2+ release using a modified Othmer-Tang-model. An increase in the period and a reduction in the amplitude of Ca2+ wave activity are obtained when increases in SERCA density are simulated while keeping all other parameters of the model constant. However, Ca2+ wave period can be reduced and the wave amplitude and velocity can be significantly increased when an increase in the luminal ER Ca2+ concentration due to SERCA overexpression is incorporated into the model. Increased luminal Ca2+ occurs because increased SERCA activity lowers cytosolic Ca2+, which is partially replenished by Ca2+ influx across the plasma membrane. These simulations are supported by experimental data demonstrating higher luminal Ca2+ levels, decreased periods, increased amplitude, and increased velocity of Ca2+ waves in response to increased SERCA density.