Two-dimensional system dynamics of cytosolic and mitochondrial calcium in a obese hepatocyte cell

Abstract

Calcium (\(\hbox {Ca}^{2+}\)) store and mitochondria play very important role in cell signaling. Despite extensive inquiry into calcium dynamics across diverse cell types, including hepatocytes, comprehension of the interconnected dynamics of cytosolic and mitochondrial calcium in normal and obese cellular milieus remains rudimentary. Calcium influx can manifest as either a transient blip or a more sustained puff, contingent upon cellular conditions. A puff, which is formed when several \(\hbox {IP}_{3}\) receptors open simultaneously, is larger than a blip, which is a tiny signal produced by a single \(\hbox {IP}_{3}\) receptor (IP3R) opening. These occurrences demonstrate cell’s capacity to regulate \(\hbox {Ca}^{2+}\) signaling precisely and vary from opening of a single channel (blip) to coordinated opening of several channels in a cluster (puff). One-dimensional model proposed by earlier researchers is able to incorporate the effect of only point source like blip but are not capable of providing effects of line sources like puffs. Higher dimensional model development is required to gain a deeper understanding of the local effects of different mechanisms and feedbacks in hepatocyte cells. Thus, a two-dimensional model for hepatocytes under normal and obese conditions, integrating a reaction-diffusion equation to delineate coupled dynamics of cytosolic and mitochondrial calcium, encompassing blip and puff phenomena has been proposed in this paper. Additionally, the ramifications of \(\hbox {Ca}^{2+}\) signaling on ATP generation and degradation rates, alongside the open channel probability of chloride and potassium ions has been investigated. Numerical simulations are executed employing the linear finite element method, spatially and Crank-Nicolson method, temporally. Furthermore, a comparative assessment of \(\hbox {Ca}^{2+}\) signaling, ATP generation, degradation rates and open channel probability of chloride and potassium ions in normal versus obese hepatocytes has been done.

Graphical abstract