Adherens junction engagement regulates functional patterning of the cardiac pacemaker cell lineage

Kandace Thomas; Trevor Henley; Simone Rossi; M Joseph Costello; William Polacheck; Boyce E Griffith; Michael Bressan

doi:10.1016/j.devcel.2021.04.004

Adherens junction engagement regulates functional patterning of the cardiac pacemaker cell lineage

Dev Cell. 2021 May 17;56(10):1498-1511.e7. doi: 10.1016/j.devcel.2021.04.004. Epub 2021 Apr 22.

Authors

Kandace Thomas¹, Trevor Henley¹, Simone Rossi², M Joseph Costello³, William Polacheck⁴, Boyce E Griffith⁵, Michael Bressan⁶

Affiliations

¹ Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Department of Mathematics, University of North Carolina, Chapel Hill, NC, USA.
³ Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; University of North Carolina at Chapel Hill and North Carolina State University, Joint Department of Biomedical Engineering, Chapel Hill, NC 27599, USA.
⁵ McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Departments of Mathematics, Applied Physical Sciences, and Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA; Carolina Center for Interdisciplinary Applied Mathematics, University of North Carolina, Chapel Hill, NC, USA; Computational Medicine Program, University of North Carolina, Chapel Hill, NC, USA.
⁶ Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: michael_bressan@med.unc.edu.

Abstract

Cardiac pacemaker cells (CPCs) rhythmically initiate the electrical impulses that drive heart contraction. CPCs display the highest rate of spontaneous depolarization in the heart despite being subjected to inhibitory electrochemical conditions that should theoretically suppress their activity. While several models have been proposed to explain this apparent paradox, the actual molecular mechanisms that allow CPCs to overcome electrogenic barriers to their function remain poorly understood. Here, we have traced CPC development at single-cell resolution and uncovered a series of cytoarchitectural patterning events that are critical for proper pacemaking. Specifically, our data reveal that CPCs dynamically modulate adherens junction (AJ) engagement to control characteristics including surface area, volume, and gap junctional coupling. This allows CPCs to adopt a structural configuration that supports their overall excitability. Thus, our data have identified a direct role for local cellular mechanics in patterning critical morphological features that are necessary for CPC electrical activity.

Keywords: adherens junction; cardiac development; cardiac pacemaker cell; cytoarchitecture; electrophysiology; gap junction; sinoatrial node.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adherens Junctions / metabolism*
Adherens Junctions / ultrastructure
Animals
Biological Clocks / physiology*
Biomechanical Phenomena
Body Patterning*
Cell Lineage*
Cell Size
Chickens
Computer Simulation
Electrophysiological Phenomena
Gap Junctions / metabolism
Heart / embryology
Heart / physiology*
Membrane Proteins
Myocardium / metabolism
Myocardium / ultrastructure
Phenotype

Substances

Membrane Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding