Effect of variations in gap junctional coupling on the frequency of oscillatory action potentials in a smooth muscle syncytium

Shailesh Appukuttan, Keith Brain, Rohit Manchanda

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Abstract

Gap junctions provide pathways for intercellular communication between adjacent cells, allowing exchange of ions and small molecules. Based on the constituent protein subunits, gap junctions are classified into different subtypes varying in their properties such as unitary conductances, sensitivity to transjunctional voltage, and gating kinetics. Gap junctions couple cells electrically, and therefore the electrical activity originating in one cell can affect and modulate the electrical activity in adjacent cells. Action potentials can propagate through networks of such electrically coupled cells, and this spread is influenced by the nature of gap junctional coupling. Our study aims to computationally explore the effect of differences in gap junctional properties on oscillating action potentials in electrically coupled tissues. Further, we also explore variations in the biophysical environment by altering the size of the syncytium, the location of the pacemaking cell, as well as the occurrence of multiple pacemaking cells within the same syncytium. Our simulation results suggest that the frequency of oscillations is governed by the extent of coupling between cells and the gating kinetics of different gap junction subtypes. The location of pacemaking cells is found to alter the syncytial behavior, and when multiple oscillators are present, there exists an interplay between the oscillator frequency and their relative location within the syncytium. Such variations in the frequency of oscillations can have important implications for the physiological functioning of syncytial tissues.
Original languageEnglish
Article number655225
Number of pages12
JournalFrontiers in Physiology
Volume12
DOIs
Publication statusPublished - 1 Oct 2021

Bibliographical note

Funding Information:
We would like to thank Rohan Sathe (IIT Bombay, India) for his inputs in modeling of the various gap junction subtypes.

Funding Information:
This work was supported by grants from the Department of Biotechnology (DBT), India (BT/PR12973/MED/122/47/2016) and the UK IERI (UKUTP20110055).

Publisher Copyright:
© Copyright © 2021 Appukuttan, Brain and Manchanda.

Keywords

  • action potential
  • gap junction
  • oscillation
  • Frequency
  • coupling

ASJC Scopus subject areas

  • Urology
  • Physiology (medical)
  • Endocrine and Autonomic Systems

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