Ultrastructure of primary pacemaking cells in rabbit sino-atrial node cells indicates limited sarcoplasmic reticulum content.

Ramesh Iyer,Oliver Monfredi,Clara Franzini-Armstrong,Mark Terasaki,Manuela Lavorato

doi:10.1096/fba.2018-00079

Abstract

The main mammalian heart pacemakers are spindle‐shaped cells compressed into tangles within protective layers of collagen in the sino‐atrial node (SAN). Two cell types, “dark” and “light,” differ on their high or low content of intermediate filaments, but share scarcity of myofibrils and a high content of glycogen. Sarcoplasmic reticulum (SR) is scarce. The free SR (fSR) occupies 0.04% of the cell volume within ~0.4 µm wide peripheral band. The junctional SR (jSR), constituting peripheral couplings (PCs), occupies 0.03% of the cell volume. Total fSR + jSR volume is 0.07% of cell volume, lower than the SR content of ventricular myocytes. The average distance between PCs is 7.6 µm along the periphery. On the average, 30% of the SAN cells surfaces is in close proximity to others. Identifiable gap junctions are extremely rare, but small sites of close membrane‐to‐membrane contacts are observed. Possibly communication occurs via these very small sites of contact if conducting channels (connexons) are located within them. There is no obvious anatomical detail that might support ephaptic coupling. These observations have implications for understanding of SAN cell physiology, and require incorporation into biophysically detailed models of SAN cell behavior that currently do not include such features.

Highlights

The pacemaking rhythm that controls the overall beating rate of the heart in health originates in the sino-atrial node (SAN)
As one moves away from this central region, there is a transition in the properties of spontaneous action potentials produced by the cells and in Abbreviations: Free Sarcoplasmic reticulum (SR), junctional SR; PC, peripheral coupling; RyR, Ryanodine receptor; SAN, Sino-atrial node; SR, sarcoplasmic reticulum
A well-defined calcium wave could be suggested to be at the basis of the observed calcium signals in isolated cells

Summary

| INTRODUCTION

The pacemaking rhythm that controls the overall beating rate of the heart in health originates in the sino-atrial node (SAN). The SAN is comprised of an anatomically and functionally heterogeneous collection of cells all capable of spontaneously and rhythmically generating action potentials, demonstrating the key property of automaticity.[1,2] Among these, the most highly specialized SAN cells are the leading or dominant pacemakers, those with the fastest rate of diastolic depolarization under a given set of physiological parameters They are located in the central region of the SAN and are the least anatomically developed cells, with the lowest density of organelles, myofibrils.[3] As one moves away from this central region, there is a transition in the properties of spontaneous action potentials produced by the cells and in Abbreviations: Free SR, junctional SR; PC, peripheral coupling; RyR, Ryanodine receptor; SAN, Sino-atrial node; SR, sarcoplasmic reticulum. It turns out that the cells have much smaller SR components than previously assumed, certainly when compared to ventricular myocytes, so initial modeling based on data from ventricle may need to be reconsidered for these SAN cells

| MATERIALS AND METHODS

| RESULTS

| DISCUSSION

Findings

| LIMITATIONS