A minimal model for the mitochondrial rapid mode of Ca²+ uptake mechanism. PLoS One 2011;6(6):e21324
Date
07/07/2011Pubmed ID
21731705Pubmed Central ID
PMC3121760DOI
10.1371/journal.pone.0021324Scopus ID
2-s2.0-79959573906 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
Mitochondria possess a remarkable ability to rapidly accumulate and sequester Ca²⁺. One of the mechanisms responsible for this ability is believed to be the rapid mode (RaM) of Ca²⁺ uptake. Despite the existence of many models of mitochondrial Ca²⁺ dynamics, very few consider RaM as a potential mechanism that regulates mitochondrial Ca²⁺ dynamics. To fill this gap, a novel mathematical model of the RaM mechanism is developed herein. The model is able to simulate the available experimental data of rapid Ca²⁺ uptake in isolated mitochondria from both chicken heart and rat liver tissues with good fidelity. The mechanism is based on Ca²⁺ binding to an external trigger site(s) and initiating a brief transient of high Ca²⁺ conductivity. It then quickly switches to an inhibited, zero-conductive state until the external Ca²⁺ level is dropped below a critical value (∼100-150 nM). RaM's Ca²⁺- and time-dependent properties make it a unique Ca²⁺ transporter that may be an important means by which mitochondria take up Ca²⁺ in situ and help enable mitochondria to decode cytosolic Ca²⁺ signals. Integrating the developed RaM model into existing models of mitochondrial Ca²⁺ dynamics will help elucidate the physiological role that this unique mechanism plays in mitochondrial Ca²⁺-homeostasis and bioenergetics.
Author List
Bazil JN, Dash RKAuthor
Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Chickens
Computer Simulation
Kinetics
Mitochondria, Heart
Mitochondria, Liver
Models, Biological
Rats
Rats, Sprague-Dawley
Time Factors