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Physiology (Bethesda, Md.) Nov 2014The sarcoplasmic reticulum (SR) is crucial for contraction and relaxation of the mammalian cardiomyocyte, but its role in other vertebrate classes is equivocal. Recent... (Review)
Review
The sarcoplasmic reticulum (SR) is crucial for contraction and relaxation of the mammalian cardiomyocyte, but its role in other vertebrate classes is equivocal. Recent evidence suggests differences in SR function across species may have an underlying structural basis. Here, we discuss how SR recruitment relates to the structural organization of the cardiomyocyte to provide new insight into the evolution of cardiac design and function in vertebrates.
Topics: Animals; Biological Evolution; Body Temperature Regulation; Calcium; Calcium Channels; Excitation Contraction Coupling; Humans; Myocardial Contraction; Myocytes, Cardiac; Sarcoplasmic Reticulum; Species Specificity
PubMed: 25362639
DOI: 10.1152/physiol.00015.2014 -
Philosophical Transactions of the Royal... Nov 2022Bird cardiomyocytes are long, thin and lack transverse (t)-tubules, which is akin to the cardiomyocyte morphology of ectothermic non-avian reptiles, who are typified by... (Review)
Review
Bird cardiomyocytes are long, thin and lack transverse (t)-tubules, which is akin to the cardiomyocyte morphology of ectothermic non-avian reptiles, who are typified by low maximum heart rates and low pressure development. However, birds can achieve greater contractile rates and developed pressures than mammals, whose wide cardiomyocytes contain a dense t-tubular network allowing for uniform excitation-contraction coupling and strong contractile force. To address this apparent paradox, this paper functionally links recent electrophysiological studies on bird cardiomyocytes with decades of ultrastructure measurements. It shows that it is the strong transsarcolemmal Ca influx via the L-type Ca current () and the high gain of Ca-induced Ca release from the sarcoplasmic reticulum (SR), coupled with an internal SR Ca release relay system, that facilitates the strong fast contractions in the long thin bird cardiomyocytes, without the need for t-tubules. The maintenance of an elongated myocyte morphology following the post-hatch transition from ectothermy to endothermy in birds is discussed in relation to cardiac load, myocyte ploidy, and cardiac regeneration potential in adult cardiomyocytes. Overall, the paper shows how little we know about cellular Ca dynamics in the bird heart and suggests how increased research efforts in this area would provide vital information in our quest to understand the role of myocyte architecture in the evolution of the vertebrate heart. This article is part of the theme issue 'The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease'. Please see glossary at the end of the paper for definitions of specialized terms.
Topics: Animals; Birds; Calcium; Mammals; Myocytes, Cardiac; Sarcoplasmic Reticulum; Vertebrates
PubMed: 36189815
DOI: 10.1098/rstb.2021.0332 -
Circulation Research Mar 2022
Topics: Calcium Signaling; Oxidative Stress; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum
PubMed: 35239403
DOI: 10.1161/CIRCRESAHA.122.320798 -
The Journal of Biological Chemistry Apr 2013The sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a transmembrane ion transporter belonging to the P(II)-type ATPase family. It performs the vital task of... (Review)
Review
The sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a transmembrane ion transporter belonging to the P(II)-type ATPase family. It performs the vital task of re-sequestering cytoplasmic Ca(2+) to the sarco/endoplasmic reticulum store, thereby also terminating Ca(2+)-induced signaling such as in muscle contraction. This minireview focuses on the transport pathways of Ca(2+) and H(+) ions across the lipid bilayer through SERCA. The ion-binding sites of SERCA are accessible from either the cytoplasm or the sarco/endoplasmic reticulum lumen, and the Ca(2+) entry and exit channels are both formed mainly by rearrangements of four N-terminal transmembrane α-helices. Recent improvements in the resolution of the crystal structures of rabbit SERCA1a have revealed a hydrated pathway in the C-terminal transmembrane region leading from the ion-binding sites to the cytosol. A comparison of different SERCA conformations reveals that this C-terminal pathway is exclusive to Ca(2+)-free E2 states, suggesting that it may play a functional role in proton release from the ion-binding sites. This is in agreement with molecular dynamics simulations and mutational studies and is in striking analogy to a similar pathway recently described for the related sodium pump. We therefore suggest a model for the ion exchange mechanism in P(II)-ATPases including not one, but two cytoplasmic pathways working in concert.
Topics: Animals; Binding Sites; Calcium; Cytosol; Humans; Ion Transport; Molecular Dynamics Simulation; Protons; Rabbits; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 23400778
DOI: 10.1074/jbc.R112.436550 -
Acta Biochimica Polonica 2003In this article the morphology of sarcoplasmic reticulum, classification of Ca(2+)-ATPase (SERCA) isoenzymes presented in this membrane system, as well as their topology... (Review)
Review
In this article the morphology of sarcoplasmic reticulum, classification of Ca(2+)-ATPase (SERCA) isoenzymes presented in this membrane system, as well as their topology will be reviewed. The focus is on the structure and interactions of Ca(2+)-ATPase determined by electron and X-ray crystallography, lamellar X-ray and neutron diffraction analysis of the profile structure of Ca(2+)-ATPase in sarcoplasmic reticulum multilayers. In addition, targeting of the Ca(2+)-ATPase to the sarcoplasmic reticulum is discussed.
Topics: Amino Acid Sequence; Animals; Calcium-Transporting ATPases; Crystallization; Crystallography, X-Ray; Humans; Models, Molecular; Molecular Sequence Data; Protein Conformation; Sarcoplasmic Reticulum
PubMed: 12833162
DOI: No ID Found -
Biochimica Et Biophysica Acta May 2011This review focuses on muscle disorders and diseases caused by defects in the Ca(2+) release channels of the sarcoplasmic reticulum, the ryanodine receptors, and in the... (Review)
Review
This review focuses on muscle disorders and diseases caused by defects in the Ca(2+) release channels of the sarcoplasmic reticulum, the ryanodine receptors, and in the luminal, low affinity, high capacity Ca(2+)-binding proteins, calsequestrins. It provides a time line over the past half century of the highlights of research on malignant hyperthermia (MH), central core disease (CCD) and catecholaminergic polymorphic ventricular tachycardia (CPVT), that resulted in the identification of the ryanodine receptor (RYR), calsequestrin (CASQ) and dihydropyridine receptor (CACNA1S) genes as sites of disease-causing mutations. This is followed by a description of approaches to functional analysis of the effects of disease-causing mutations on protein function, focusing on studies of how mutations affect spontaneous (store overload-induced) Ca(2+)-release from the sarcoplasmic reticulum, the underlying cause of MH and CPVT. Subsequent sections describe results obtained by analysis of knockin mouse lines carrying MH- and CCD-causing mutations, including a Casq1 knockout. The review concludes with the presentation of two mechanistic models. The first shows how dysregulation of Ca(2+) homeostasis can lead to muscle diseases involving both RyR and Casq proteins. The second describes a theory of central core formation wherein non-uniformity of Ca(2+) release, resulting in non-uniformity of muscle contraction, is presented as an intrinsic property of the specific tertiary structure of mutant heterotetrameric ryanodine receptors and as the underlying cause of core formation in skeletal muscle. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
Topics: Animals; Calcium Signaling; Humans; Models, Biological; Muscular Diseases; Mutation; Penetrance; Sarcoplasmic Reticulum
PubMed: 21118704
DOI: 10.1016/j.bbamcr.2010.11.009 -
The Journal of Physiology Aug 2015
Topics: Animals; Calcium Signaling; Congresses as Topic; Humans; Sarcoplasmic Reticulum
PubMed: 26228552
DOI: 10.1113/jphysiol.2014.281907 -
Cardiovascular Research May 2013Cardiac excitation-contraction coupling occurs primarily at the sites of transverse (T)-tubule/sarcoplasmic reticulum junctions. The orderly T-tubule network guarantees... (Review)
Review
Cardiac excitation-contraction coupling occurs primarily at the sites of transverse (T)-tubule/sarcoplasmic reticulum junctions. The orderly T-tubule network guarantees the instantaneous excitation and synchronous activation of nearly all Ca(2+) release sites throughout the large ventricular myocyte. Because of the critical roles played by T-tubules and the array of channels and transporters localized to the T-tubule membrane network, T-tubule architecture has recently become an area of considerable research interest in the cardiovascular field. This review will focus on the current knowledge regarding normal T-tubule structure and function in the heart, T-tubule remodelling in the transition from compensated hypertrophy to heart failure, and the impact of T-tubule remodelling on myocyte Ca(2+) handling function. In the last section, we discuss the molecular mechanisms underlying T-tubule remodelling in heart disease.
Topics: Animals; Calcium; Cardiomegaly; Excitation Contraction Coupling; Heart Failure; Humans; Myocytes, Cardiac; Sarcoplasmic Reticulum
PubMed: 23393229
DOI: 10.1093/cvr/cvt020 -
Sarcoplasmic Reticulum Structure and Functional Properties that Promote Long-Lasting Calcium Sparks.Biophysical Journal Jan 2016Calcium (Ca) sparks are the fundamental sarcoplasmic reticulum (SR) Ca release events in cardiac myocytes, and they have a typical duration of 20-40 ms. However, when a...
Calcium (Ca) sparks are the fundamental sarcoplasmic reticulum (SR) Ca release events in cardiac myocytes, and they have a typical duration of 20-40 ms. However, when a fraction of ryanodine receptors (RyRs) are blocked by tetracaine or ruthenium red, Ca sparks lasting hundreds of milliseconds have been observed experimentally. The fundamental mechanism underlying these extremely prolonged Ca sparks is not understood. In this study, we use a physiologically detailed mathematical model of subcellular Ca cycling to examine how Ca spark duration is influenced by the number of functional RyRs in a junctional cluster (which is reduced by tetracaine or ruthenium red) and other SR Ca handling properties. One RyR cluster contains a few to several hundred RyRs, and we use a four-state Markov RyR gating model. Each RyR opens stochastically and is regulated by cytosolic and luminal Ca. We varied the number of functional RyRs in the single cluster, diffusion within the SR network, diffusion between network and junctional SR, cytosolic Ca diffusion, SERCA uptake activity, and RyR open probability. For long-lasting Ca release events, opening events within the cluster must occur continuously because the typical open time of the RyR is only a few milliseconds. We found the following: 1) if the number of RyRs is too small, it is difficult to maintain consecutive openings and stochastic attrition terminates the release; 2) if the number of RyRs is too large, the depletion of Ca from the junctional SR terminates the release; and 3) very long release events require relatively small-sized RyR clusters (reducing flux as seen experimentally with tetracaine) and sufficiently rapid intra-SR Ca diffusion, such that local junctional intra-SR [Ca] can be maintained by intra-SR diffusion and overall SR Ca reuptake.
Topics: Animals; Calcium Signaling; Humans; Ion Channel Gating; Kinetics; Models, Theoretical; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 26789761
DOI: 10.1016/j.bpj.2015.12.009 -
Advances in Experimental Medicine and... 2013Cardiovascular disease is a leading cause of death worldwide, with ischemic heart disease alone accounting for >12% of all deaths, more than HIV/AIDS, tuberculosis,... (Review)
Review
Cardiovascular disease is a leading cause of death worldwide, with ischemic heart disease alone accounting for >12% of all deaths, more than HIV/AIDS, tuberculosis, lung, and breast cancer combined. Heart disease has been the leading cause of death in the United States for the past 85 years and is a major cause of disability and health-care expenditures. The cardiac conditions most likely to result in death include heart failure and arrhythmias, both a consequence of ischemic coronary disease and myocardial infarction, though chronic hypertension and valvular diseases are also important causes of heart failure. Sodium-calcium exchange (NCX) is the dominant calcium (Ca2+) efflux mechanism in cardiac cells. Using ventricular-specific NCX knockout mice, we have found that NCX is also an essential regulator of cardiac contractility independent of sarcoplasmic reticulum Ca2+ load. During the upstroke of the action potential, sodium (Na+) ions enter the diadic cleft space between the sarcolemma and the sarcoplasmic reticulum. The rise in cleft Na+, in conjunction with depolarization, causes NCX to transiently reverse. Ca2+ entry by this mechanism then "primes" the diadic cleft so that subsequent Ca2+ entry through Ca2+ channels can more efficiently trigger Ca2+ release from the sarcoplasmic reticulum. In NCX knockout mice, this mechanism is inoperative (Na+ current has no effect on the Ca2+ transient), and excitation-contraction coupling relies upon the elevated diadic cleft Ca2+ that arises from the slow extrusion of cytoplasmic Ca2+ by the ATP-dependent sarcolemmal Ca2+ pump. Thus, our data support the conclusion that NCX is an important regulator of cardiac contractility. These findings suggest that manipulation of NCX may be beneficial in the treatment of heart failure.
Topics: Animals; Calcium; Female; Heart Failure; Humans; Male; Mice; Mice, Knockout; Muscle Proteins; Myocardial Contraction; Myocardium; Sarcoplasmic Reticulum; Sodium-Calcium Exchanger
PubMed: 23224894
DOI: 10.1007/978-1-4614-4756-6_30