Developmental Cell
Volume 56, Issue 10, 17 May 2021, Pages 1498-1511.e7
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Article
Adherens junction engagement regulates functional patterning of the cardiac pacemaker cell lineage

https://doi.org/10.1016/j.devcel.2021.04.004Get rights and content
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Highlights

  • Adherens junction (AJ) engagement impacts cardiac pacemaker cell (CPC) excitability

  • Blocking AJ formation is sufficient to generate CPC-like morphological features

  • AJ formation induces gap junction trafficking to the plasma membrane in CPCs

  • FLRT3 is a cell-autonomous regulator of CPC cytoarchitecture

Summary

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

sinoatrial node
cardiac pacemaker cell
adherens junction
electrophysiology
gap junction
cytoarchitecture
cardiac development

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