Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15196-201. doi: 10.1073/pnas.1411557111. Epub 2014 Oct 6.

Defects in T-tubular electrical activity underlie local alterations of calcium release in heart failure.

Author information

1
European Laboratory for Non-Linear Spectroscopy, 50019 Florence, Italy;
2
Division of Pharmacology, Department "NeuroFarBa," University of Florence, 50139 Florence, Italy;
3
Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy;
4
R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030;
5
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.
6
European Laboratory for Non-Linear Spectroscopy, 50019 Florence, Italy; National Institute of Optics, National Research Council, 50125 Florence, Italy sacconi@lens.unifi.it.

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.

KEYWORDS:

calcium imaging; cardiac disease; nonlinear microscopy; voltage imaging

PMID:
25288764
PMCID:
PMC4210349
DOI:
10.1073/pnas.1411557111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center