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Biophysical Journal 85:1474-1481 (2003)
© 2003 The Biophysical Society

Modeling the Dependence of the Period of Intracellular Ca2+ Waves on SERCA Expression

Martin Falcke *, Yun Li {dagger}, James D. Lechleiter {ddagger} and Patricia Camacho {dagger}

* Hahn Meitner Institute, 14109 Berlin, Germany; and {dagger} Departments of Physiology and {ddagger} Cellular & Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229

Correspondence: Address reprint requests to Martin Falcke, Hahn Meitner Institute, Glienicker Str. 100, 14109 Berlin, Germany. E-mail: falcke{at}hmi.de.

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.




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