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A minimal model for the mitochondrial rapid mode of Ca²+ uptake mechanism. PLoS One 2011;6(6):e21324

Date

07/07/2011

Pubmed ID

21731705

Pubmed Central ID

PMC3121760

DOI

10.1371/journal.pone.0021324

Scopus ID

2-s2.0-79959573906 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

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 RK

Author

Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Chickens
Computer Simulation
Kinetics
Mitochondria, Heart
Mitochondria, Liver
Models, Biological
Rats
Rats, Sprague-Dawley
Time Factors