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 Lab Nonlinear Spect, I-50019 Florence, Italy; CNR, Natl Inst Opt, I-50125 Florence, Italy; Univ Florence, Div Pharmacol, Dept NeuroFarBa, I-50139 Florence, Italy; Univ Florence, Div Physiol, Dept Expt & Clin Med, I-50134 Florence, Italy; Univ Connecticut, RD Berlin Ctr Cell Anal & Modeling, Ctr Hlth, Farmington, CT 06030 USA; Univ Florence, Dept Phys & Astron, I-50019 Sesto Fiorentino, 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´s Horizon 2020 research and innovation programme under grant agreement no 654148 Laserlab-Europe. This research project has been also supported by the National Institutes of Health (NIH Grant: R01 EB001963), by the Italian Ministry for Education, University and Research in the framework of the Flagship Project NANOMAX, by the Italian Ministry of Health (WFR GR-2011-02350583), by Telethon-Italy (GGP13162), by Ente Cassa di Risparmio di Firenze (private foundation), and by Regione Toscana (PAR-FAS Salute 2014, “TORSADE” project).
KeyWords: heart failure; T-tubules; excitation-contraction coupling; -adrenergic signalling; non-linear microscopy imaging
DOI: 10.3390/ijms17091471

Citations: 10
data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2024-11-17
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