Mitochondrial and sarcolemmal Ca2+ transport reduce [Ca2+]i during caffeine contractures in rabbit cardiac myocytes.

Bassani, Rosana A.; Bassani, José Wilson Magalhães; Bers, Donald M.

doi:10.1113/jphysiol.1992.sp019246

Cited by 216 publications

(198 citation statements)

References 44 publications

Supporting

Mentioning

179

Contrasting

Unclassified

Order By: Relevance

“…In a parallel study from the lab of Hajnoczky, Pacher et al [147] calculated that ∼26% of the Ca 2+ released from the SR after caffeineexposure was taken up by mitochondria. This contrasts to the 1% of Ca 2+ removed by mitochondria after SR Ca 2+ release as calculated by Bassani et al [9].…”

Section: Evidence For a Mitochondrial Ca 2+ Microdomaincontrasting

confidence: 70%

“…One of the first quantitative estimations of mitochondrial Ca 2+ uptake during EC coupling comes from a study by Bassani et al [9]. The aim of that study was to calculate the relative contribution of SR Ca 2+ -ATPase, NCX, PMCA and mitochondria for cytosolic Ca 2+ removal after a rapid release of Ca 2+ from the SR.…”

Section: Evidence Against Fast Mitochondrial Ca 2+ Uptakementioning

confidence: 99%

“…The remaining decay was attributed to Ca 2+ removal by mitochondria and the PMCA, since it was blocked by mitochondrial uncoupling (by application of FCCP and oligomycin 5 s prior to the caffeine pulse) or inhibition of PMCA, each contributing about equally to the Ca 2+ removal rate [9]. Thus, the relative contributions of SR Ca 2+ -ATPase, NCX, PMCA and mitochondria to diastolic Ca 2+ -removal in rabbit ventricular myocytes were 70%,28%,1% and 1% [9,14,15].This implies that under steady-state conditions, 70% of Ca 2+ cycle into and out of the SR, whereas ∼29% enter the cell via L-type Ca 2+ channels and leave the cell via the NCX and PMCA. Consequently, only 1% of Ca 2+ would enter and leave mitochondria on every beat.…”

Section: Evidence Against Fast Mitochondrial Ca 2+ Uptakementioning

confidence: 99%

“…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. However, regarding the controversy on the amount of Ca 2+ taken up by mitochondria during EC coupling [9,117,147], the definite relevance of mitochondrial Ca 2+ uptake for cytosolic Ca 2+ homeostasis is still incompletely understood.…”

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

confidence: 99%

“…Since in the persistent presence of caffeine, the SR Ca 2+ -ATPase cannot refill the SR, the decay of [Ca 2+ ] c was achieved primarily by forward-mode I NCX . Consequently, with 0 Na + and 0 Ca 2+ in the extracellular solution (to inhibit I NCX ), the decay of [Ca 2+ ] c was substantially slowed [9]. The remaining decay was attributed to Ca 2+ removal by mitochondria and the PMCA, since it was blocked by mitochondrial uncoupling (by application of FCCP and oligomycin 5 s prior to the caffeine pulse) or inhibition of PMCA, each contributing about equally to the Ca 2+ removal rate [9].…”

mentioning

confidence: 99%

See 4 more Smart Citations

Excitation-contraction coupling and mitochondrial energetics

Maack

O’Rourke²

2007

Basic Res Cardiol

221

183

View full text Add to dashboard Cite

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...

show abstract

Section: Evidence For a Mitochondrial Ca 2+ Microdomaincontrasting

confidence: 70%

Section: Evidence Against Fast Mitochondrial Ca 2+ Uptakementioning

confidence: 99%

Section: Evidence Against Fast Mitochondrial Ca 2+ Uptakementioning

confidence: 99%

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

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Excitation-contraction coupling and mitochondrial energetics

Maack

O’Rourke²

2007

Basic Res Cardiol

221

183

View full text Add to dashboard Cite

show abstract

The Cardiac Na ⁺ ‐Ca ²⁺ Exchanger: From Structure to Function

Ottolia

John²,

Hazan

et al. 2021

Comprehensive Physiology

View full text Add to dashboard Cite

Ca 2+ homeostasis is essential for cell function and survival. As such, the cytosolic Ca 2+ concentration is tightly controlled by a wide number of specialized Ca 2+ handling proteins. One among them is the Na + -Ca 2+ exchanger (NCX), a ubiquitous plasma membrane transporter that exploits the electrochemical gradient of Na + to drive Ca 2+ out of the cell, against its concentration gradient. In this critical role, this secondary transporter guides vital physiological processes such as Ca 2+ homeostasis, muscle contraction, bone formation, and memory to name a few.Herein, we review the progress made in recent years about the structure of the mammalian NCX and how it relates to function. Particular emphasis will be given to the mammalian cardiac isoform, NCX1.1, due to the extensive studies conducted on this protein. Given the degree of conservation among the eukaryotic exchangers, the information highlighted herein will provide a foundation for our understanding of this transporter family. We will discuss gene structure, alternative splicing, topology, regulatory mechanisms, and NCX's functional role on cardiac physiology. Throughout this article, we will attempt to highlight important milestones in the field and controversial topics where future studies are required.

show abstract