Propagation of Ca2+ release in cardiac myocytes: Role of mitochondria

Seguchi, Hidetaka; Ritter, Michael; Shizukuishi, Masaaki; Ishida, Hideyuki; Genka, Chokoh; Nakazawa, Hiroe; Spitzer, Kenneth W.; Barry, William H.

doi:10.1016/j.ceca.2005.03.004

Cited by 40 publications

(34 citation statements)

References 29 publications

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“…When blocking mitochondrial Ca 2+ uptake, an increase of cytosolic Ca 2+ transients was observed ( Fig. 6E and F; [100,117,124,171]). It also appears that the highly organized pattern of mitochondria localized close to the SR provides a "local control" of SR Ca 2+ release events.…”

Section: Implications Of Rapid Mitochondrial Ca 2+ Uptake For Ec Coupmentioning

confidence: 90%

“…Several studies indicate that by buffering [Ca 2+ ] c , rapid mitochondrial Ca 2+ uptake directly affects EC coupling [61,100,117,119,124,147,148,171]. When blocking mitochondrial Ca 2+ uptake, an increase of cytosolic Ca 2+ transients was observed ( Fig.…”

Section: Implications Of Rapid Mitochondrial Ca 2+ Uptake For Ec Coupmentioning

confidence: 95%

“…In the following years, a number of studies attempted to measure mitochondrial Ca 2+ uptake during EC coupling more directly, with quite controversial results [12,26,33,[59][60][61]68,[72][73][74]100,117,119,136,137,140,141,144,147,148,161,170,171,176,191,200,201,213] [26,117,119,148,176,191,200,201] or fluo-3 [33,144,170]) penetrate sarcolemmal and mitochondrial membranes and accumulate (to different degrees) in the mitochondrial matrix. To avoid contamination of the fluorescence signal by cytosolic Ca 2+ , the groups of Hansford, Silverman [59,60,74,136,137] and Bers [26,222] applied MnCl 2 in the extracellular solution.…”

Section: Evidence Against Fast Mitochondrial Ca 2+ Uptakementioning

confidence: 99%

“…The propagation of caffeine-induced Ca 2+ sparks was suppressed by mitochondria, since inhibition of the mCU (with Ru360) resulted in regenerative Ca 2+ waves across the whole cell [171]. Similarly, in atrial myocytes, where cytosolic Ca 2+ transients occur primarily in the periphery due to the lack of t-tubules, uptake of Ca 2+ into mitochondria and the SR prevented the propagation of the peripheral Ca 2+ transients to more central parts of the cell [119], even though the density of mitochondria is lower in atrial than in ventricular cells [171]. Taken together, these results suggest that mitochondria may function as spatial buffers for Ca 2+ , regulating the propagation of Ca 2+ release events and thus, contractility of the cell.…”

Section: Implications Of Rapid Mitochondrial Ca 2+ Uptake For Ec Coupmentioning

confidence: 99%

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Excitation-contraction coupling and mitochondrial energetics

Maack

O’Rourke²

2007

Basic Res Cardiol

221

183

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Cardiac excitation-contraction (EC) coupling consumes vast amounts of cellular energy, most of which is produced in mitochondria by oxidative phosphorylation. In order to adapt the constantly varying workload of the heart to energy supply, tight coupling mechanisms are essential to maintain cellular pools of ATP, phosphocreatine and NADH. To our current knowledge, the most important regulators of oxidative phosphorylation are ADP, P i , and Ca 2+ . However, the kinetics of mitochondrial Ca 2+ -uptake during EC coupling are currently a matter of intense debate. Recent experimental findings suggest the existence of a mitochondrial Ca 2+ microdomain in cardiac myocytes, justified by the close proximity of mitochondria to the sites of cellular Ca 2+ release, i. e., the ryanodine receptors of the sarcoplasmic reticulum. Such a Ca 2+ microdomain could explain seemingly controversial results on mitochondrial Ca 2+ uptake kinetics in isolated mitochondria versus whole cardiac myocytes. Another important consideration is that rapid mitochondrial Ca 2+ uptake facilitated by microdomains may shape cytosolic Ca 2+ signals in cardiac myocytes and have an impact on energy supply and demand matching. Defects in EC coupling in chronic heart failure may adversely affect mitochondrial Ca 2+ uptake and energetics, initiating a vicious cycle of contractile dysfunction and energy depletion. Future therapeutic approaches in the treatment of heart failure could be aimed at interrupting this vicious cycle. Keywords calcium; sodium; microdomain; heart failure; adenosine triphosphate; adenosine diphosphate; respiration; tricarboxylic acid cycle Physiological aspectsThe most important function of the heart is to pump blood to supply the body with oxygen and substrates. In order to adapt cardiac output to the constantly changing demand of blood supply, the heart utilizes three major mechanisms to increase cardiac output: the force-frequency relationship (the Bowditch effect or Treppe; [22]), the Frank-Starling mechanism (sarcomere length-dependent activation of contractile force) [66,149,164], and sympathetic activation [28]. All of these mechanisms increase and accelerate myocardial force generation, and at the same time increase cellular energy demand. By these mechanisms, cardiac output during exertion can be increased more than five-fold compared to resting conditions. © Steinkopff Verlag 2007Correspondence to: Christoph Maack. NIH Public Access Excitation-contraction couplingOf fundamental importance for cardiac contraction and relaxation are the processes of excitation-contraction (EC) coupling (Fig. 1). During the action potential (AP), voltage-gated Na + -channels are activated, and the inward Na + -current (I Na ) induces a rapid depolarization of the cell membrane, facilitating voltage-dependent opening of L-type Ca 2+ -channels (I Ca,L ). The Ca 2+ influx triggers the opening of the ryanodine receptor (RyR2 subtype), inducing the release of even greater amounts of Ca 2+ from the sarcoplasmic reticulum (SR), a process te...

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Section: Implications Of Rapid Mitochondrial Ca 2+ Uptake For Ec Coupmentioning

confidence: 90%

Section: Implications Of Rapid Mitochondrial Ca 2+ Uptake For Ec Coupmentioning

confidence: 95%

Section: Evidence Against Fast Mitochondrial Ca 2+ Uptakementioning

confidence: 99%

Section: Implications Of Rapid Mitochondrial Ca 2+ Uptake For Ec Coupmentioning

confidence: 99%

See 2 more Smart Citations

Excitation-contraction coupling and mitochondrial energetics

Maack

O’Rourke²

2007

Basic Res Cardiol

221

183

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“…concentration (Seguchi et al, 2005) or exposure of cells to pro-oxidant agents 16 (Park et al, 2006). Furthermore, this model depends on contractile activity of the cells as neither mPTP opening nor cell death was observed in the absence of electrical stimulation.…”

Section: +mentioning

confidence: 99%

Oxidative stress, mitochondrial permeability transition pore opening and cell death during hypoxia–reoxygenation in adult cardiomyocytes

Assaly¹,

Tassigny²,

Paradis³

et al. 2012

European Journal of Pharmacology

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Abstract:Reactive oxygen species production is necessary to induce cell death following hypoxia/reoxygenation but the effect of reactive oxygen species produced during hypoxia on mitochondrial permeability transition pore (mPTP) opening and cell death is not established. Here we designed a model of hypoxia/reoxygenation in isolated cardiomyocytes measuring simultaneously reactive oxygen species production, mPTP opening and cell death in order (i) to establish a causal relationship between them, (ii) to investigate the roles of various reactive oxygen species in mPTP opening. The percentage of cardiomyocytes exhibiting mPTP opening during reoxygenation increased with the duration of hypoxia. Antioxidants increased the time to mPTP opening when present during hypoxia but not at reoxygenation. This was associated with a drop in hydroxyl radical and hydrogen peroxide during hypoxia and the first minutes of reoxygenation. The increase in time to mPTP opening was accompanied by an improvement in cell viability reflected by maintenance of superoxide production at reoxygenation. Cyclosporin A delayed both the time to mPTP opening and cell death despite maintenance of reactive oxygen species production during hypoxia. These findings demonstrate that reactive oxygen species production precedes mPTP opening and that reactive oxygen species produced during hypoxia, particularly hydroxyl radicals and hydrogen peroxide, are necessary to induce mPTP opening which depends on hypoxia duration.

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Modeling calcium regulation of contraction, energetics, signaling, and transcription in the cardiac myocyte

Winslow

Walker

Greenstein

2015

WIREs Mechanisms of Disease

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Calcium (Ca(2+)) plays many important regulatory roles in cardiac muscle cells. In the initial phase of the action potential, influx of Ca(2+) through sarcolemmal voltage-gated L-type Ca(2+) channels (LCCs) acts as a feed-forward signal that triggers a large release of Ca(2+) from the junctional sarcoplasmic reticulum (SR). This Ca(2+) drives heart muscle contraction and pumping of blood in a process known as excitation-contraction coupling (ECC). Triggered and released Ca(2+) also feed back to inactivate LCCs, attenuating the triggered Ca(2+) signal once release has been achieved. The process of ECC consumes large amounts of ATP. It is now clear that in a process known as excitation-energetics coupling, Ca(2+) signals exert beat-to-beat regulation of mitochondrial ATP production that closely couples energy production with demand. This occurs through transport of Ca(2+) into mitochondria, where it regulates enzymes of the tricarboxylic acid cycle. In excitation-signaling coupling, Ca(2+) activates a number of signaling pathways in a feed-forward manner. Through effects on their target proteins, these interconnected pathways regulate Ca(2+) signals in complex ways to control electrical excitability and contractility of heart muscle. In a process known as excitation-transcription coupling, Ca(2+) acting primarily through signal transduction pathways also regulates the process of gene transcription. Because of these diverse and complex roles, experimentally based mechanistic computational models are proving to be very useful for understanding Ca(2+) signaling in the cardiac myocyte.

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Propagation of Ca2+ release in cardiac myocytes: Role of mitochondria

Cited by 40 publications

References 29 publications

Excitation-contraction coupling and mitochondrial energetics

Excitation-contraction coupling and mitochondrial energetics

Oxidative stress, mitochondrial permeability transition pore opening and cell death during hypoxia–reoxygenation in adult cardiomyocytes

Modeling calcium regulation of contraction, energetics, signaling, and transcription in the cardiac myocyte

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