Interplay Between Sub-Cellular Alterations of Calcium Release and T-Tubular Defects in Cardiac Diseases

Year: 2018

Authors: Scardigli M., Ferrantini C., Crocini C., Pavone F.S., Sacconi L.

Autors Affiliation: National Institute of Optics, National Research Council, Florence, Italy; European Laboratory for Non-Linear Spectroscopy, Florence, Italy; Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Department of Molecular, Cellular, and Developmental Biology & BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, United States; Department of Physics and Astronomy, University of Florence, Florence, Italy

Abstract: Asynchronous Ca2+ release promotes non-homogeneous myofilament activation, leading to mechanical dysfunction, as well as initiation of propagated calcium waves and arrhythmias. Recent advances in microscopy techniques have allowed for optical recordings of local Ca2+ fluxes and action potentials from multiple sub-cellular domains within cardiac cells with unprecedented spatial and temporal resolution. Since then, sub-cellular local information of the spatio-temporal relationship between Ca2+ release and action potential propagation have been unlocked, providing novel mechanistic insights in cardiac excitation-contraction coupling (ECC). Here, we review the promising perspectives arouse from repeatedly probing Ca2+ release at the same sub-cellular location while simultaneously probing multiple locations at the same time within a single cardiac cell. We also compare the results obtained in three different rodent models of cardiac diseases, highlighting disease-specific mechanisms. Slower local Ca2+ release has been observed in regions with defective action potential conduction in diseased cardiac cells. Moreover, significant increment of Ca2+ variability (both in time and in space) has been found in diseased cardiac cells but does not directly correlate with local electrical defects nor with the degree of structural aberrations of the cellular membrane system, suggesting a role for other players of the ECC machinery. We finally explore exciting opportunities provided by the technology for studying different cardiomyocyte populations, as well as for dissecting the mechanisms responsible for subcellular spatio-temporal variability of Ca2+ release.

Journal/Review: FRONTIERS IN PHYSIOLOGY

Volume: 9      Pages from: 1474-1  to: 1474-10

More Information: This work was supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 654148 Laserlab-Europe, by the Italian Ministry for Education, University and Research in the framework of the Flagship Project NanoMAX, by the Italian Ministry of Health (WFR GR-2011-02350583), by Telethon-Italy (GGP13162), by Ente Cassa di Risparmio di Firenze (private foundation), and by FAS-Salute ToRSADE project. CC holds a long-term fellowship from the Human Frontiers Science Program Organization (LT001449/2017-L).
KeyWords: t-tubule; excitation-contraction coupling; calcium imaging; voltage imaging; microscopy
DOI: 10.3389/fphys.2018.01474

ImpactFactor: 3.201
Citations: 10
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