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 Camacho and Lechleiter 1993 . Here we examine these experimental findings by modeling Ca2 release using a modified Othmer Tang model Tang and others 1996, Falcke and others 1999 . 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 since 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 densit