Studying dyadic structure-function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling.

Excitation--contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transie...

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Publicado en:Clinical Medicine Insights: Cardiology Vol. 11; pp. 1 - 12
Autores principales: Maleckar, Mary M., Edwards, Andrew G., Louch, William E., Lines, Glenn T.
Formato: pictorial review tables/charts Journal Article
Publicado: Sage Publications Inc. 2017
Acceso en línea:Ver este registro en EBSCOhost
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      jtl: Clinical Medicine Insights: Cardiology
      issn: 11795468
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    pubinfo:
      dt: 2017
      vid: 11
      pid: 344
      pub: Sage Publications Inc.
      place: Thousand Oaks, California
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        atl: Studying dyadic structure-function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling.
      aug:
        au:
          Maleckar, Mary M.
          Edwards, Andrew G.
          Louch, William E.
          Lines, Glenn T.
        affil: Simula Research Laboratory, Center for Cardiological Innovation and Center for Biomedical Computing, Lysaker, Norway
      sug:
        subj:
          Cardiovascular System Physiology
          Electrophysiology
          Myocytes, Cardiac Physiopathology
          Calcium Physiology
          Calcium Metabolism
          Models, Structural
          Models, Biological
          Computer Simulation
      ab: Excitation--contraction coupling in cardiac myocytes requires calcium influx through L-type calcium channels in the sarcolemma, which gates calcium release through sarcoplasmic reticulum ryanodine receptors in a process known as calcium-induced calcium release, producing a myoplasmic calcium transient and enabling cardiomyocyte contraction. The spatio-temporal dynamics of calcium release, buffering, and reuptake into the sarcoplasmic reticulum play a central role in excitation--contraction coupling in both normal and diseased cardiac myocytes. However, further quantitative understanding of these cells' calcium machinery and the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease requires accurate knowledge of cardiac ultrastructure, protein distribution and subcellular function. As current imaging techniques are limited in spatial resolution, limiting insight into changes in calcium handling, computational models of excitation--contraction coupling have been increasingly employed to probe these structure--function relationships. This review will focus on the development of structural models of cardiac calcium dynamics at the subcellular level, orienting the reader broadly towards the development of models of subcellular calcium handling in cardiomyocytes. Specific focus will be given to progress in recent years in terms of multi-scale modeling employing resolved spatial models of subcellular calcium machinery. A review of the state-of-the-art will be followed by a review of emergent insights into calcium-dependent etiologies in heart disease and, finally, we will offer a perspective on future directions for related computational modeling and simulation efforts.
      pubtype: Academic Journal
      doctype:
        pictorial
        review
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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