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Int. J. Mol. Sci. 2016, 17(9), 1471;

T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure

European Laboratory for Non-Linear Spectroscopy, Florence 50019, Italy
National Institute of Optics, National Research Council, Florence 50125, Italy
Division of Pharmacology, Department “NeuroFarBa”, University of Florence, Florence 50139, Italy
Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, 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, Sesto Fiorentino 50019, Italy
Author to whom correspondence should be addressed.
Academic Editors: H. W. M. Niessen and Paul A. J. Krijnen
Received: 12 July 2016 / Revised: 17 August 2016 / Accepted: 30 August 2016 / Published: 3 September 2016
(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure 2017)
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Alterations of the β-adrenergic signalling, structural remodelling, and electrical failure of T-tubules are hallmarks of heart failure (HF). Here, we assess the effect of β-adrenoceptor activation on local Ca2+ release in electrically coupled and uncoupled T-tubules in ventricular myocytes from HF rats. We employ an ultrafast random access multi-photon (RAMP) microscope to simultaneously record action potentials and Ca2+ transients from multiple T-tubules in ventricular cardiomyocytes from a HF rat model of coronary ligation compared to sham-operated rats as a control. We confirmed that β-adrenergic stimulation increases the frequency of Ca2+ sparks, reduces Ca2+ transient variability, and hastens the decay of Ca2+ transients: all these effects are similarly exerted by β-adrenergic stimulation in control and HF cardiomyocytes. Conversely, β-adrenergic stimulation in HF cells accelerates a Ca2+ rise exclusively in the proximity of T-tubules that regularly conduct the action potential. The delayed Ca2+ rise found at T-tubules that fail to conduct the action potential is instead not affected by β-adrenergic signalling. Taken together, these findings indicate that HF cells globally respond to β-adrenergic stimulation, except at T-tubules that fail to conduct action potentials, where the blunted effect of the β-adrenergic signalling may be directly caused by the lack of electrical activity. View Full-Text
Keywords: heart failure; T-tubules; excitation-contraction coupling; β-adrenergic signalling; non-linear microscopy imaging heart failure; T-tubules; excitation-contraction coupling; β-adrenergic signalling; non-linear microscopy imaging

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Crocini, C.; Coppini, R.; Ferrantini, C.; Yan, P.; Loew, L.M.; Poggesi, C.; Cerbai, E.; Pavone, F.S.; Sacconi, L. T-Tubular Electrical Defects Contribute to Blunted β-Adrenergic Response in Heart Failure. Int. J. Mol. Sci. 2016, 17, 1471.

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