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Monday, July 20 • 9:00pm - 10:00pm
P123: Computational Implementation in NEURON of Inter-cellular Calcium Waves in Syncytial Tissue

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Nilapratim Sengupta, Rohit Manchanda
Session Link: https://meet.google.com/vym-dbzi-puw
Calcium plays highly critical roles in various physiological processes such as muscle contraction, neurotransmission, cell growth and proliferation. Intracellular calcium handling mechanisms have been studied extensively. However, concepts of intracellular calcium dynamics must be complemented with the knowledge of calcium spread in tissues where neighbouring cells are coupled to each other forming a syncytium. Intercellular calcium waves (ICW) are ‘complex spatiotemporal events’ essentially comprising of an elevated level of intracellular calcium that appears to spread from the initiating/stimulated cell to the coupled neighbours [1]. Gap junction mediated diffusion has been identified as a crucial mechanism for ICW in syncytial tissues [2].

The complex structure of syncytial tissue, coupled with different signalling molecules and their varied mechanisms of involvement makes it difficult to study ICW from a quantitative point of view using in vitro or in vivo experiments. Though mathematical models describing ICW propagation in two- dimensions exist, there is no report of a biophysical model to account for three dimensional propagation of ICW in vivo in syncytial tissues. A key objective of our work was to realize, using the NEURON platform, a model for 3-D propagation. Several computational labs (primarily working on neural networks) make use of this platform to build models. However to our knowledge, in none of the existing cellular network models has chemical coupling of cells been incorporated. Successful implementation of our developed technique would produce a biophysically detailed model incorporating structural, electrical as well as chemical aspects that could be used to upgrade all existing models once suitable changes in parameters are made.

Gap junctions, in the NEURON platform, have usually been modelled as low resistance electrical shunts between connected cells [3]. In a novel approach we modelled the gap junction such as to enable it to transfer calcium between connected cells, based on the ion’s electro-chemical gradient. We have equipped the detrusor smooth muscle cell model with intracellular calcium handling mechanisms and then modified the gap junctional connection to incorporate intercellular calcium flow, besides non-specific current. We have successfully simulated calcium spread from the source cell to its adjoining neighbours and beyond. Within the network, as the distance from the source cell increases, extent of calcium flow diminishes as it propagates due to diffusion, buffering and its being pumped out of the cells (Fig. 1).

Our model is in a preliminary stage and is yet to be tuned. Literature pertaining to ICW in detrusor is scant. Hence the model would need to be tuned in terms of overall cellular response, with active ion channels integrated. Subsequently, techniques mimicking messenger regeneration would need to be incorporated, besides passive diffusion.

References:

1. Leybaert, L., & Sanderson, M. J. (2012). Intercellular Ca2+ waves: mechanisms and function. Physiological Reviews, 92(3), 1359-1392.

2. Sanderson, M. J., Charles, A. C., & Dirksen, E. R. (1990). Mechanical stimulation and intercellular communication increases intracellular Ca2+ in epithelial cells. Cell Regulation, 1(8), 585.

3. Appukuttan S., Brain K. L. & Manchanda R. (2015). A computational model of urinary bladder smooth muscle syncytium. Journal of Computational Neuroscience, 38(1), 167-187.




Speakers
NS

Nilapratim Sengupta

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay
Computational Neuroscience



Monday July 20, 2020 9:00pm - 10:00pm CEST
Slot 20