T-Tubular Electrical Defects Contribute to Blunted beta-Adrenergic Response in Heart Failure
Authors: Crocini C., Coppini R., Ferrantini C., Yan P., Loew L. M., Poggesi C., Cerbai E., Pavone F.S., Sacconi L.
Autors Affiliation: 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
Abstract: Alterations of the -adrenergic signalling, structural remodelling, and electrical failure of T-tubules are hallmarks of heart failure (HF). Here, we assess the effect of -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 -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 -adrenergic stimulation in control and HF cardiomyocytes. Conversely, -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 -adrenergic signalling. Taken together, these findings indicate that HF cells globally respond to -adrenergic stimulation, except at T-tubules that fail to conduct action potentials, where the blunted effect of the -adrenergic signalling may be directly caused by the lack of electrical activity.
Journal/Review: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume: 17 Pages from: 1471-1 to: 1471-10
More Information: This project has received funding from the European UnionKeyWords: heart failure; T-tubules; excitation-contraction coupling; -adrenergic signalling; non-linear microscopy imagingDOI: 10.3390/ijms17091471Citations: 6data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2019-10-20References taken from IsiWeb of Knowledge: (subscribers only)Connecting to view paper tab on IsiWeb: Click hereConnecting to view citations from IsiWeb: Click here