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.
Highlights
Cells in certain kinds of tissues, such as cardiac and smooth muscle, are known to be electrically coupled to adjacent cells, thereby forming an electrical syncytium (Eisenberg et al, 1979)
We first present the effect of variations in the extent of gap junctional coupling between cells on the frequency of oscillations, irrespective of the gap junction subtype
The extent of gap junctional coupling between each pair of adjacent cells in the 1-D model was varied over a wide range of conductance levels
Summary
Cells in certain kinds of tissues, such as cardiac and smooth muscle, are known to be electrically coupled to adjacent cells, thereby forming an electrical syncytium (Eisenberg et al, 1979) These intercellular connections are formed by means of protein structures known as gap junctions. The extent of spatial spread is determined by various factors such as the unitary conductance, sensitivity to transjunctional voltage and gating kinetics These factors are known to vary based on the constituent protein sub-units, known as connexins, forming the gap junction. Homomeric refers to the presence of only a single connexin subtype in a hemi-channel, as opposed to heteromeric indicating multiple connexin subtypes, and homotypic refers to both hemi-channels being identical, in contrast to heterotypic where the two hemi-channels are different Within each of these classes, there exists a wide diversity in biophysical behavior based on the nature of the specific connexins involved. These differences in the nature of intercellular coupling between cells holds huge potential to influence tissue functioning
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