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.
Falcke
Martin
M
Hahn Meitner Institute, 14109 Berlin, Germany. falcke@hmi.de
Li
Yun
Y
Lechleiter
James D
JD
Camacho
Patricia
P
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D015153:Blotting, Western; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000737:chemistry*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007700:Kinetics; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D015233:Models, Statistical; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013997:Time Factors; D014981:Xenopus
D012333:RNA, Messenger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium