title: β-Adrenergic response is counteracted by extremely-low-frequency pulsed electromagnetic fields in beating cardiomyocytes.
abstract: 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, Ca(2+) 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.
authors.affiliation: Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Cornacchione
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy; Institute of Cell Biology and Neurobiology (IBCN), National Research Council (CNR), Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fassina
authors.affiliation: Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy.
authors.forename: Maria Evelina
authors.initials: ME
authors.lastname: Mognaschi
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Di Siena
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gimmelli
authors.affiliation: Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ambrosino
authors.affiliation: Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.
authors.forename: Maria Virginia
authors.initials: MV
authors.lastname: Soldovieri
authors.affiliation: Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Taglialatela
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Gianfrilli
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Isidori
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy. Electronic address: fabio.naro@uniroma1.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Naro
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D004574:Electromagnetic Fields; D004734:Energy Metabolism / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects / Q000528:radiation effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D002118:Calcium
keywords: Ca(2+) transients; Chronotropy; ELF-PEMF; Hypertrophy; βARs