β-Adrenergic response is counteracted by extremely-low-frequency pulsed electromagnetic fields in beating cardiomyocytes.


Author: Cornacchione M1, Pellegrini M2, Fassina L3, Mognaschi ME3, Di Siena S4, Gimmelli R4, Ambrosino P1, Soldovieri MV1, Taglialatela M1, Gianfrilli D5, Isidori AM5, Lenzi A5, Naro F6

Affiliation: <sup>1</sup>Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.

<sup>2</sup>Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy; Institute of Cell Biology and Neurobiology (IBCN), National Research Council (CNR), Rome, Italy.

<sup>3</sup>Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.

<sup>4</sup>Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.

<sup>5</sup>Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

<sup>6</sup>Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy. Electronic address: fabio.naro@uniroma1.it.
Conference/Journal: J Mol Cell Cardiol.
Date published: 2016 Jul 11
Other:
  Pages: S0022-2828(16)30224-3   ,  Special Notes: doi: 10.1016/j.yjmcc.2016.07.004. [Epub ahead of print]   ,  Word Count: 272  
    Proper β-adrenergic signaling is indispensable for modulating heart frequency. Studies on extremely-low-frequency pulsed electromagnetic field (ELF-PEMF) effects in the heart beat function are contradictory and no definitive conclusions were obtained so far. To investigate the interplay between ELF-PEMF exposure and β-adrenergic signaling, cultures of primary murine neonatal cardiomyocytes and of sinoatrial node were exposed to ELF-PEMF and short and long-term effects were evaluated. The ELF-PEMF generated a variable magnetic induction field of 0-6mT at a frequency of 75Hz. Exposure to 3mT ELF-PEMF induced a decrease of contraction rate, Ca2+ transients, contraction force, and energy consumption both under basal conditions and after β-adrenergic stimulation in neonatal cardiomyocytes. ELF-PEMF exposure inhibited β-adrenergic response in sinoatrial node (SAN) region. ELF-PEMF specifically modulated β2 adrenergic receptor response and the exposure did not modify the increase of contraction rate after adenylate cyclase stimulation by forskolin. In HEK293T cells transfected with β1 or β2 adrenergic receptors, ELF-PEMF exposure induced a rapid and selective internalization of β2 adrenergic receptor. The β-adrenergic signaling, was reduced trough Gi protein by ELF-PEMF exposure since the phosphorylation level of phospholamban and the PI3K pathway were impaired after isoproterenol stimulation in neonatal cardiomyocytes. Long term effects of ELF-PEMF exposure were assessed in cultures of isolated cardiomyocytes. ELF-PEMF counteracts cell size increase, the generation of binucleated of cardiomyocytes and prevents the up-regulation of hypertrophic markers after β-adrenergic stimulation, indicating an inhibition of cell growth and maturation. These data show that short and long term exposure to ELF-PEMF induces a reduction of cardiac β-adrenergic response at molecular, functional and adaptative levels.



Copyright © 2016. Published by Elsevier Ltd.



KEYWORDS: Ca(2+) transients; Chronotropy; ELF-PEMF; Hypertrophy; βARs



PMID: 27418252  DOI: 10.1016/j.yjmcc.2016.07.004