Scientific Results

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

Year: 2016

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 (9)      Pages from: 1471-1  to: 1471-10

More Information: This project has received funding from the European Union
KeyWords: heart failure; T-tubules; excitation-contraction coupling; -adrenergic signalling; non-linear microscopy imaging
DOI: 10.3390/ijms17091471

Citations: 8
data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2021-11-28
References taken from IsiWeb of Knowledge: (subscribers only)
Connecting to view paper tab on IsiWeb: Click here
Connecting to view citations from IsiWeb: Click here

gdpr-image
This site uses cookies. If you decide to continue browsing we consider that you accept their use. For more information about cookies and how to delete them please read our Info Policy on cookies use.
Read more