Investigating the ultrastructure of the atrial dyad in health and disease

Abstract

The contraction is the major function of the cardiac muscle, the atrial and ventricles are playing a major role in cardiac contraction. The atria are the two upper chambers and the two lower chambers are known as ventricles, they consist of cardiac myocytes (cardiac cells). This research highlights the atrial myocytes for large mammals such as sheep. The myocytes include transverse tubules (t-tubules), sarcoplasmic reticulum (SR), Caveolae and dyad, they influence the excitation-contraction coupling (ECC) by releasing calcium (Ca2+) to the cytosol to initiate the ECC, this interaction is called Ca2+ induced Ca2+ released (CICR). This is started by the neuron signals that send to the cardiac muscle and initiate the action potential, it influences the Ca2+ entry through tubular L-type Ca2+ channels (LTCCs), which stimulates the ryanodine Receptors (RyRs) in the SR membrane. The efficiency of this process is based on the density and size of the dyad. On the other hand, the Ca2+ extrusion also occurs by the t-tubule via the Na+/Ca2+ exchanger (NCX). In contrast, the heart failure (HF) causes an alteration in cardiac myocytes. For instance, the disorganization of t-tubules structure, impact the SR size and the dyad density and size. All these alterations disrupt the ECC by reducing the Ca2+ influx and promote impaired contractility and arrhythmogenesis in cardiac disease. The aims of this study to determine (i) the alteration of the t-tubules, SR, caveolae and dyad of atrial myocytes in HF, (ii) The dyad size and density, (iii) The dyad formation in HF for atrial myocytes. The methods and results for this project, the samples of the atria were collected from adult female sheep, electron microscopic (EM) images were taken for sheep arterial myocytes to examine and clarify the t-tubules, SR, caveolae and dyad function for the contraction during HF. The measurements were calculated by using the IMOD. The results are the HF cells have numerous caveolae on the surface (sarcolemma), disorganization in the SR and t-tubules structure. The t-tubules disappear in the middle of the cell, the Ca2+ located near to the sarcolemma but it disappears from the middle. The dyad formation occurs near the sarcolemma, which means the Ca2+ is released into the cell in HF states. Lower size and density of dyad comparing with control. The SR quantity was high in the middle of the cell comparing with the site next to the sarcolemma. To summarise, The atrial and ventricles myocytes are both important in the ECC. The t-tubules has been found in sheep for both the atrial and ventricles. Recent works have worked on the ventricular myocytes to determine the alteration during the HF, our aim is to focus on the atrial myocytes and investigate if it has similar changes or differences.