Spatio temporal interdependent calcium and buffer dynamics regulating DAG in a hepatocyte cell due to obesity.

Abstract

Calcium ions (Ca²⁺) serve as a crucial signaling mechanism in almost all cells. The buffers are proteins that bind free Ca²⁺ to reduce the cell's Ca²⁺ concentration. The most studies reported in the past on calcium signaling in various cells have considered the buffer concentration as constant in the cell. However, buffers also diffuse and their concentration varies dynamically in the cells. Almost no work has been reported on interdependent calcium and buffer dynamics in the cells. In the present study, a model is proposed for inter-dependent spatio-temporal dynamics of calcium and buffer by coupling reaction-diffusion equations of Ca²⁺ and buffer in a hepatocyte cell. Boundary and initial conditions are framed based on the physiological state of the cell. The effect of various parameters viz. inositol 1,4,5-triphosphate receptor (IP3R), diffusion coefficient, SERCA pump and ryanodine receptor (RyR) on spatio-temporal dynamics of calcium and buffer regulating diacylglycerol (DAG) in a normal and obese hepatocyte cell has been studied using finite element simulation. From the results, it is concluded that the dynamics of calcium and buffer impact each other significantly along the spatio-temporal dimensions, thereby affecting the regulation of all the processes including DAG in a hepatocyte cell. The proposed model is more realistic than the existing ones, as the interdependent system dynamics of calcium and buffer have different regulatory impacts as compared to the individual and independent dynamics of these signaling processes in a hepatocyte cell.