The low conductance mitochondrial permeability transition pore confers excitability and CICR wave propagation in a computational model

Oster, Andrew M.; Thomas, Balbir; Terman, David; Fall, Christopher P.

doi:10.1016/j.jtbi.2010.12.023

Cited by 24 publications

(32 citation statements)

References 41 publications

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“…This simplified model successfully simulates all mCICR profiles observed experimentally, as well as the notable triggering characteristics of mCICR (82). To better understand the role of mPTP in the propagation of waves of depolarization and Ca 2ϩ release, Oster et al (70) modified the Magnus-Keizer model (55)(56)(57) by incorporating the PTP (75,82) and mitochondrial pH buffering systems. In their model, the low conductance mPTP opening (PTP l ) is assumed to be initialized by pH changes (H m ).…”

Section: Mitochondrial Excitability Induced By Mptp-mediated Mitochonmentioning

confidence: 97%

“…However, the application of this powerful tool to the study of mitochondrial network excitability has only recently begun. In this short review, we describe several recently published models of mitochondrial network excitability and oscillations that are based on observations of ROS-or Ca 2ϩ -induced ⌬⌿ m depolarization (70,72,96,98). These computational studies provide additional evidence to support the concept of mitochondrial network excitability.…”

Section: Introductionmentioning

confidence: 99%

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Cardiac mitochondrial network excitability: insights from computational analysis

Zhou

O’Rourke

2012

American Journal of Physiology-Heart and Circulatory Physiology

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In the heart, mitochondria form a regular lattice and function as a coordinated, nonlinear network to continuously produce ATP to meet the high-energy demand of the cardiomyocytes. Cardiac mitochondria also exhibit properties of an excitable system: electrical or chemical signals can spread within or among cells in the syncytium. The detailed mechanisms by which signals pass among individual elements (mitochondria) across the network are still not completely understood, although emerging studies suggest that network excitability might be mediated by the local diffusion and autocatalytic release of messenger molecules such as reactive oxygen species and/or Ca(2+). In this short review, we have attempted to described recent advances in the field of cardiac mitochondrial network excitability. Specifically, we have focused on how mitochondria communicate with each other through the diffusion and regeneration of messenger molecules to initiate and propagate waves or oscillations, as revealed by computational models of mitochondrial network.

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Section: Mitochondrial Excitability Induced By Mptp-mediated Mitochonmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Cardiac mitochondrial network excitability: insights from computational analysis

Zhou

O’Rourke

2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…The only factor able to change transmembrane potential ∆Ψ m is the massive efflux of the matrix contents (in particular Ca 2+ ions) through PTPs. Though some papers consider the outflow of calcium through PTPs (in low conductance state) [4], [10], it seems that PTPs opening takes place extremely rarely and mainly under stress conditions e.g. in the process of apoptosis [38].…”

Section: The Mathematical Modelmentioning

confidence: 99%

“…Sarco-endoplasmic reticulum Ca 2+ ATPase (SERCA) pumps calcium from the cytosol to the lumen of ER, while IP 3 R or ryanodine receptors (RyR) release calcium from the ER stores. Voltagedependent anion channels (VDAC) on outer mitochondrial membrane and uniporters on the internal mitochondrial membrane (IMM) allow Ca 2+ to reach mitochondrial matrix along the electro-chemical gradient [3], [4]. Ca 2+ can exit mitochondria through specific exchangers located on the internal mitochondrial membrane, which remove calcium from the matrix to the perimitochondrial space, which…”

Section: Introductionmentioning

confidence: 99%

Membrane associated complexes : new approach to calcium dynamics modelling

Dyzma

Szopa

Kaźmierczak

2012

Math. Model. Nat. Phenom.

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Abstract. Mitochondria are one of the most important organelles determining Ca 2+ regulatory pathway in the cell. Recent experiments suggested the existence of cytosolic microdomains with locally elevated calcium concentration (CMDs) in the nearest vicinity of the outer mitochondrial membrane (OMM). These intermediate physical connections between endoplasmic reticulum (ER) and mitochodria are called MAM (mitochondria-associated ER membrane) complexes.The aim of this paper is to take into account the direct calcium flow from ER to mitochondria implied by the existence of MAMs and perform detailed numerical analysis of the influence of this flow on the type and shape of calcium oscillations. Depending on the permeability of MAMs interface and ER channels, different patterns of oscillations appear (simple, bursting and chaotic). For some parameters the oscillatory pattern disappear and the system tends to a steady state with extremely high calcium level in mitochondria, which can be interpreted as a crucial point at the beginning of an apoptotic pathway.

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“…(Fall and Keizer 2001) extended the work of Magnus and Keizer (1997;1998a;b) to show Ca 2+ stimulation of mitochondrial metabolism in ATP production and the interplay between mitochondrial and ER calcium signaling. Recently, Oster et al (2011) extended the modular Magnus-Keizer computational model for respiration −driven Ca 2+ handling to include a permeability transition based on a channel-like pore mechanism. They also determined both the excitability and Ca 2+ wave propagation based on CICR mechanism.…”

Section: Introductionmentioning

confidence: 99%

Modelling mechanism of calcium oscillations in pancreatic acinar cells

Manhas

Pardasani

2014

J Bioenerg Biomembr

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We present a simple model for calcium oscillations in the pancreatic acinar cells. This model is based on the calcium release from two receptors, inositol trisphosphate receptors (IPR) and ryanodine receptors (RyR) through the process of calcium induced calcium release (CICR). In pancreatic acinar cells, when the Ca²⁺ concentration increases, the mitochondria uptake it very fast to restrict Ca(2+) response in the cell. Afterwards, a much slower release of Ca²⁺ from the mitochondria serves as a calcium supply in the cytosol which causes calcium oscillations. In this paper we discuss a possible mechanism for calcium oscillations based on the interplay among the three calcium stores in the cell: the endoplasmic reticulum (ER), mitochondria and cytosol. Our model predicts that calcium shuttling between ER and mitochondria is a pacemaker role in the generation of Ca²⁺ oscillations. We also consider the calcium dependent production and degradation of (1,4,5) inositol-trisphosphate (IP3), which is a key source of intracellular calcium oscillations in pancreatic acinar cells. In this study we are able to predict the different patterns of calcium oscillations in the cell from sinusoidal to raised-baseline, high frequency and low-frequency baseline spiking.

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The low conductance mitochondrial permeability transition pore confers excitability and CICR wave propagation in a computational model

Cited by 24 publications

References 41 publications

Cardiac mitochondrial network excitability: insights from computational analysis

Cardiac mitochondrial network excitability: insights from computational analysis

Membrane associated complexes : new approach to calcium dynamics modelling

Modelling mechanism of calcium oscillations in pancreatic acinar cells

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