Proarrhythmic atrial ectopy associated with heart sympathetic innervation dysfunctions is specific for murine B6CBAF1 hybrid strain.

Autor: Kuzmin VS; Lomonosov Moscow State University, Biological Faculty, Department of Human and Animal Physiology, Leninskie gory 1, building 12, 119991 Moscow, Russia; Pirogov Russian National Research Medical University (RNRMU), Ostrovitjanova 1, 117997 Moscow, Russia., Potekhina VM; Lomonosov Moscow State University, Biological Faculty, Department of Human and Animal Physiology, Leninskie gory 1, building 12, 119991 Moscow, Russia. Electronic address: vm-potekhina@yandex.ru., Odnoshivkina YG; Department of Normal Physiology, Kazan State Medical University, Kazan, Russia., Chelombitko MA; The A.N. Belozersky Institute of Physico-Chemical Biology, MSU, Moscow, Russia., Fedorov AV; Lomonosov Moscow State University, Biological Faculty, Department of Human and Animal Physiology, Leninskie gory 1, building 12, 119991 Moscow, Russia., Averina OA; The A.N. Belozersky Institute of Physico-Chemical Biology, MSU, Moscow, Russia; Institute of Functional Genomics, Lomonosov Moscow State University, Moscow, Russia., Borodkov AS; Vernadsky Institute of Geochemistry and Analytical Chemistry of Russian Academу of Sciences, Moscow, Russia., Shevtsova AA; Lomonosov Moscow State University, Faculty of Biology, Department of Genetics, Moscow, Russia., Lovat ML; Lomonosov Moscow State University, Biological Faculty, Department of Human and Animal Physiology, Leninskie gory 1, building 12, 119991 Moscow, Russia., Petrov AM; Institute of Neuroscience, Kazan State Medial University, Kazan, Russia; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', Kazan, Russia.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Feb 01; Vol. 266, pp. 118887. Date of Electronic Publication: 2020 Dec 11.
DOI: 10.1016/j.lfs.2020.118887
Abstrakt: A lot of animal models are developed with aim to advance in atrial fibrillation (AF) understanding. The hybrid B6CBAF1 mice are used extensively as a background to create manifestation of various diseases, however, their atrial electrophysiology, autonomic sympathetic innervation of the heart and potential for AF investigation is poorly characterized. In the present study we used ECG and microelectrode recordings from multicellular atrial preparations to reveal attributes of atrial electrical activity in B6CBAF1. Also, experiments with a fluorescent false monoamine neurotransmitter and glyoxylic acid-based staining were carried out to characterize functionally and morphologically catecholaminergic innervation of the B6CBAF1 atria. Atrial myocardium of B6CBAF1 is highly prone to ectopic automaticity and exhibits abnormal spontaneous action potential accompanied by multiple postdepolarizations that result in proarrhythmic triggered activity unlike two parental C57Bl/6 and CBA strains. In vivo experiments revealed that B6CBAF1 hybrids are more susceptible to the norepinephrine induced AF. Also, sympathetic nerve terminals are partially dysfunctional in B6CBAF1 revealing lower ability to accumulate and release neurotransmitters unlike two parental strains. The analysis of the heart rate variability revealed suppressed sympathetic component of the autonomic heart control in B6CBAF1. The organization of sympathetic innervation is very similar morphologically in all three murine strains however the abundance of non-bifurcated catecholamine-positive fibers in B6CBAF1 was increased. These results suggest that B6CBAF1 mice exhibit enhanced intrinsic atrial proarrhythmicity, while the abnormalities of sympathetic neurotransmitter cycling probably underlie disturbed autonomic heart control.
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Databáze: MEDLINE