原创力文档a minimal model for the mitochondrial rapid mode of ca2+ uptake mechanism最小模型的线粒体快速模式ca2 +吸收机制.pdfVIP
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aminimalmodelforthemitochondrialrapidmodeofca2uptakemechanism最小模型的线粒体快速模式ca2吸收机制
A Minimal Model for the Mitochondrial Rapid Mode of
Ca2+ Uptake Mechanism
Jason N. Bazil, Ranjan K. Dash*
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America
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.
Citation: Bazil JN, Dash RK (2011) A Minimal Model for the Mitochondrial Rapid Mode of Ca2+ Uptake Mechanism. PLoS ONE 6(6): e21324. doi:10.1371/
journal.pone.0021324
Editor: Matjaz Perc, University of Maribor, Slovenia
Received
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