A minimal model for the mitochondrial rapid mode of Ca²+ uptake mechanism

PLoS One. 2011;6(6):e21324. doi: 10.1371/journal.pone.0021324. Epub 2011 Jun 23.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

  • Calcium