Drivers of sinoatrial node automaticity in zebrafish: comparison with mechanisms of mammalian pacemaker function

Stoyek, M. R., MacDonald, E. , Mantifel, M., Baillie, J. S., Selig, B. M., Croll, R. P., Smith, F. M. and Quinn, T. A. (2022) Drivers of sinoatrial node automaticity in zebrafish: comparison with mechanisms of mammalian pacemaker function. Frontiers in Physiology, 13, 818122. (doi: 10.3389/fphys.2022.818122) (PMID:35295582) (PMCID:PMC8919049)

Abstract

Cardiac excitation originates in the sinoatrial node (SAN), due to the automaticity of this distinct region of the heart. SAN automaticity is the result of a gradual depolarisation of the membrane potential in diastole, driven by a coupled system of transarcolemmal ion currents and intracellular Ca2+ cycling. The frequency of SAN excitation determines heart rate and is under the control of extra- and intracardiac (extrinsic and intrinsic) factors, including neural inputs and responses to tissue stretch. While the structure, function, and control of the SAN have been extensively studied in mammals, and some critical aspects have been shown to be similar in zebrafish, the specific drivers of zebrafish SAN automaticity and the response of its excitation to vagal nerve stimulation and mechanical preload remain incompletely understood. As the zebrafish represents an important alternative experimental model for the study of cardiac (patho-) physiology, we sought to determine its drivers of SAN automaticity and the response to nerve stimulation and baseline stretch. Using a pharmacological approach mirroring classic mammalian experiments, along with electrical stimulation of intact cardiac vagal nerves and the application of mechanical preload to the SAN, we demonstrate that the principal components of the coupled membrane- Ca2+ pacemaker system that drives automaticity in mammals are also active in the zebrafish, and that the effects of extra- and intracardiac control of heart rate seen in mammals are also present. Overall, these results, combined with previously published work, support the utility of the zebrafish as a novel experimental model for studies of SAN (patho-) physiological function.

• Item Type: Articles
• Additional Information: This work was supported by the Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-04879 to TQ, PGS-D to MS and EM, and USRA to MM and BS), the Heart and Stroke Foundation of Canada (G-18-0022185 to TQ), and the Canadian Institutes of Health Research (MOP 342562 to TQ).
• Keywords: Physiology, heart rate, voltage clock, calcium clock, mechanics clock, autonomic nervous system, stretch, leading pacemaker site, blebbistatin.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: MacDonald, Dr Eilidh
• Authors: Stoyek, M. R., MacDonald, E., Mantifel, M., Baillie, J. S., Selig, B. M., Croll, R. P., Smith, F. M., and Quinn, T. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Frontiers in Physiology
• Publisher: Frontiers Media
• ISSN: 1664-042X
• ISSN (Online): 1664-042X
• Copyright Holders: Copyright © 2022 Stoyek, MacDonald, Mantifel, Baillie, Selig, Croll, Smith and Quinn
• First Published: First published in Frontiers in Physiology 13: 818122
• Publisher Policy: Reproduced under a Creative Commons License