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Resistance of Embryonic Chick Atria to Inhibition of HCN-Channels and Components of the “Ca2+-Clock”

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Abstract

Despite its medical importance, the cellular mechanisms activity and the contribution of various ion channels of embryonic heart automatism are not yet fully understood. In this study we investigated the effects of specific ion-channel inhibitors on the generation of action potentials in pacemaker cells of the right atrium in chicken embryos (HH36). We used microelectrode technique and evaluated the sensitivity of pacemaker cells to ivabradine (inhibitor of HCN-channels, through which the hyperpolarization-activated current, I f), ryanodine (agonist of ryanodine receptors) and SN6 (inhibitor of Na+/Ca2+-exchange). It was found that the right atrium cells have a phase of slow diastolic depolarization. However, these cells were not sensitive to ivabradine (3 µM). We did not register significant changes in the electrophysiological parameters of action potentials. When ryanodine (1 µM) and SN6 (10 µM) were added to the perfusion solution, we observed similar effects: spontaneous rate the generation of action potential increased by 15%. Disturbance of rhythmic activity or disruption of the generation of electrical impulses were not observed in right atrial samples of chicken embryos. The obtained results allow us to conclude that, at this of embryonic development stage, HCN4-channels, ryanodine receptors, and the Na+/Ca2+-exchange are not decisive for maintaining the automatism of the right atrial cells in the chick embryo. We assume that the ion currents flowing through these channels are important in electrophysiology in adult animals, but they have a modulating function in the embryonic myocardium.

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Funding

The work was performed within the framework of the general theme of the Program of Fundamental Research of the Russian Academy of Sciences of the Laboratory of Cardiac Physiology of the Komi Science Center of the Ural Branch Russian Academy of Sciences (no. 0415-2019-0006).

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Authors and Affiliations

Authors

Contributions

Idea and research design development, planning of experiments (E.A.L., M.A.G.), conducting experimental work and processing of the obtained results (E.A.L., M.A.G.), writing and editing the text of the article (E.A.L., M.A.G.).

Corresponding author

Correspondence to E. A. Lebedeva.

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COMPLIANCE WITH ETHICAL STANDARDS

The experimental protocol complied with the international regulations Guide for the Care and Use of Laboratory Animals, 8th edition, published by National Academies Press (US), 2011 and was approved by the independent bioethics committee of the Institute of Physiology of the Komi Science Center of the Ural Branch Russian Academy of Sciences (conclusion dated December 25, 2017).

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

Additional information

Translated by A. Dyomina

Russian Text © The Author(s), 2023, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2023, Vol. 109, No. 8, pp. 1140–1148https://doi.org/10.31857/S0869813923080071.

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Lebedeva, E.A., Gonotkov, M.A. Resistance of Embryonic Chick Atria to Inhibition of HCN-Channels and Components of the “Ca2+-Clock”. J Evol Biochem Phys 59, 1452–1458 (2023). https://doi.org/10.1134/S1234567823040353

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