Defects in T-tubular electrical activity underlie local alterations of calcium release in heart failure
Authors: Crocini C., Coppini R., Ferrantini C., Yan P., Loew L.M., Tesi C., Cerbai E., Poggesi C., Pavone F.S., Sacconi L.
Autors Affiliation: European Laboratory for Non-Linear Spectroscopy, 50019 Florence, Italy; Division of Pharmacology, Department “NeuroFarBa,” University of Florence, 50139 Florence, Italy; Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy; R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030 USA; Department of Physics and Astronomy, University of Florence, 50019 Sesto Fiorentino, Italy; National Institute of Optics, National Research Council, 50125 Florence, Italy
Abstract: Action potentials (APs), via the transverse axial tubular system (TATS), synchronously trigger uniform Ca2+ release throughout the cardiomyocyte. In heart failure (HF), TATS structural remodeling occurs, leading to asynchronous Ca2+ release across the myocyte and contributing to contractile dysfunction. In cardiomyocytes from failing rat hearts, we previously documented the presence of TATS elements which failed to propagate AP and displayed spontaneous electrical activity; the consequence for Ca2+ release remained, however, unsolved. Here, we develop an imaging method to simultaneously assess TATS electrical activity and local Ca2+ release. In HF cardiomyocytes, sites where T-tubules fail to conduct AP show a slower and reduced local Ca2+ transient compared with regions with electrically coupled elements. It is concluded that TATS electrical remodeling is a major determinant of altered kinetics, amplitude, and homogeneity of Ca2+ release in HF. Moreover, spontaneous depolarization events occurring in failing T-tubules can trigger local Ca2+ release, resulting in Ca2+ sparks. The occurrence of tubuledriven depolarizations and Ca2+ sparks may contribute to the arrhythmic burden in heart failure.
Journal/Review: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume: 111 (42) Pages from: 15196 to: 15201
More Information: We thank Dr. Francesco Vanzi for useful discussion about the manuscript. The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreements 241577, 241526, and 284464. This research project was also supported by Human Frontier Science Program Research Grant RGP0027/2009, by National Institutes of Health (NIH Grant: R01 EB001963), by the Italian Ministry for Education, University and Research in the framework of the Flagship Project NANOMAX, and by Telethon-Italy (GGP13162).KeyWords: cardiac disease; voltage imaging; calcium imaging; nonlinear microscopy; DOI: 10.1073/pnas.1411557111Citations: 47data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2020-08-09References taken from IsiWeb of Knowledge: (subscribers only)Connecting to view paper tab on IsiWeb: Click hereConnecting to view citations from IsiWeb: Click here