title: Defects in T-tubular electrical activity underlie local alterations of calcium release in heart failure.
abstract: Action potentials (APs), via the transverse axial tubular system (TATS), synchronously trigger uniform Ca(2+) release throughout the cardiomyocyte. In heart failure (HF), TATS structural remodeling occurs, leading to asynchronous Ca(2+) 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 Ca(2+) release remained, however, unsolved. Here, we develop an imaging method to simultaneously assess TATS electrical activity and local Ca(2+) release. In HF cardiomyocytes, sites where T-tubules fail to conduct AP show a slower and reduced local Ca(2+) 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 Ca(2+) release in HF. Moreover, spontaneous depolarization events occurring in failing T-tubules can trigger local Ca(2+) release, resulting in Ca(2+) sparks. The occurrence of tubule-driven depolarizations and Ca(2+) sparks may contribute to the arrhythmic burden in heart failure.
authors.affiliation: European Laboratory for Non-Linear Spectroscopy, 50019 Florence, Italy;
authors.forename: Claudia
authors.initials: C
authors.lastname: Crocini
authors.affiliation: Division of Pharmacology, Department "NeuroFarBa," University of Florence, 50139 Florence, Italy;
authors.forename: Raffaele
authors.initials: R
authors.lastname: Coppini
authors.affiliation: Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy;
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ferrantini
authors.affiliation: R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030;
authors.forename: Ping
authors.initials: P
authors.lastname: Yan
authors.affiliation: R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030;
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Loew
authors.affiliation: Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy;
authors.forename: Chiara
authors.initials: C
authors.lastname: Tesi
authors.affiliation: Division of Pharmacology, Department "NeuroFarBa," University of Florence, 50139 Florence, Italy;
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
authors.affiliation: Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy;
authors.forename: Corrado
authors.initials: C
authors.lastname: Poggesi
authors.affiliation: European Laboratory for Non-Linear Spectroscopy, 50019 Florence, Italy; Department of Physics and Astronomy, University of Florence, 50019 Sesto Fiorentino, Italy; and National Institute of Optics, National Research Council, 50125 Florence, Italy.
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Pavone
authors.affiliation: European Laboratory for Non-Linear Spectroscopy, 50019 Florence, Italy; National Institute of Optics, National Research Council, 50125 Florence, Italy sacconi@lens.unifi.it.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sacconi
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D008297:Male; D032342:Muscle Cells / Q000166:cytology*; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D049452:Green Fluorescent Proteins; D002118:Calcium
keywords: calcium imaging; cardiac disease; nonlinear microscopy; voltage imaging