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Rat caval vein myocardium undergoes changes in conduction characteristics during postnatal ontogenesis

  • Molecular and cellular mechanisms of disease
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Abstract

The electrophysiological properties of the superior vena cava (SVC) myocardium, which is considered a minor source of atrial arrhythmias, were studied in this study during postnatal development. Conduction properties were investigated in spontaneously active and electrically paced SVC preparations obtained from 7–60-day-old male Wistar rats using optical mapping and microelectrode techniques. The presence of high-conductance connexin 43 (Cx43) was evaluated in SVC cross-sections using immunofluorescence. It was found that SVC myocardium is excitable, electrically coupled with the atrial tissue, and conducts excitation waves at all stages of postnatal development. However, the conduction velocity (CV) of excitation and action potential (AP) upstroke velocity in SVC were significantly lower in neonatal than in adult animals and increased with postnatal maturation. Connexins Cx43 were identified in both neonatal and adult rat SVC myocardium; however, the abundance of Cx43 was significantly less in neonates. The gap junction uncoupler octanol affected conduction more profound in the neonatal than in adult SVC. We demonstrated for the first time that the conduction characteristics of SVC myocardium change from a slow-conduction (nodal) to a high-conduction (working) phenotype during postnatal ontogenesis. An age-related CV increase may occur due to changes of AP characteristics, electrical coupling, and Cx43 presence in SVC cardiomyocyte membranes. Observed changes may contribute to the low proarrhythmicity of adult caval vein cardiac tissue, while pre- or postnatal developmental abnormalities that delay the establishment of the working conduction phenotype may facilitate SVC proarrhythmia.

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Abbreviations

AF:

Atrial fibrillation

AP:

action potential

CV:

conduction velocity

Cx43:

Connexin 43

dv/dtmax :

Maximum upstroke velocity of action potential

SAN:

Sinoatrial node

SVC:

Superior vena cava

SV:

Sinus venosus

PV:

Pulmonary vein

RA:

Right atrium

RMP:

Resting membrane potential

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Funding

The study was supported by the Russian Foundation for Basic Research (RFBR) (grant no. 18-315-00253).

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Authors and Affiliations

  1. Department of Human and Animal Physiology, Biological Faculty, Lomonosov Moscow State University, 1-12 Leninskie Gory, Moscow, Russia, 119234

    Alexandra D. Ivanova & Vlad S. Kuzmin

  2. N. N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia

    Daria V. Samoilova

  3. Ural Federal University, Institute of Natural Sciences and Mathematics, Ekaterinburg, Russia

    Artem A. Razumov

  4. Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia

    Vlad S. Kuzmin

Authors
  1. Alexandra D. Ivanova
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  2. Daria V. Samoilova
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  3. Artem A. Razumov
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  4. Vlad S. Kuzmin
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Contributions

Alexandra D. Ivanova carried out electrophysiological experiments, data analysis, and drafted the manuscript. Daria V. Samoilova performed the immunohistochemical staining. Artem A. Razumov carried out the analysis of optical mapping data. Vlad S. Kuzmin conceived and designed the study and drafted and revised the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Alexandra D. Ivanova.

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All experimental procedures were carried out in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications No. 8023, revised 1978) and approved by the Ethics Committee of the Biological faculty of MSU.

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Ivanova, A.D., Samoilova, D.V., Razumov, A.A. et al. Rat caval vein myocardium undergoes changes in conduction characteristics during postnatal ontogenesis. Pflugers Arch - Eur J Physiol 471, 1493–1503 (2019). https://doi.org/10.1007/s00424-019-02320-0

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