Modeling calcium signaling by Cellular Automata simulation incorporating endocrine regulation and trafficking in various types of receptors

Abstract

Abstract Calcium signaling plays important physiological roles which range widely from activation of muscle, synaptic transmission, cell movement, fertilization, growth in the cell population, learning process and retention of memory, to saliva secretion. Calcium also plays a crucial role in biochemical processes such as enzyme activity regulation, ion channels permeability, including activity of ion pumps, and different parts of the cytoskeleton. Signaling is initiated when the cell is stimulated, which results in the release of calcium ions (Ca2+) from intracellular stores. Many cell surface receptors, including G protein-coupled receptors, stimulate the formation of IP3 that diffuses to the endoplasmic reticulum, binds to its receptor, leading to the release of Ca2+ from the endoplasmic reticulum. Here, we construct a Cellular Automata model of signal transduction pathway mediated by calcium sensing receptors. The mechanism of receptor trafficking and dimerization is taken into account to exert positive feedback effects on the binding affinity of the cognate receptors. Difference equations are utilized to update the levels of calcium in the intracellular and extracellular compartments, incorporating endocrine regulation through the parathyroid hormone. Time series of calcium concentrations are obtained to investigate the effects of different fractions of healthy (functional) and defective receptors as well as dimerization process.

Keywords

• calcium signaling
• Cellular Automata model
• parathyroid hormone
• receptor trafficking
• dimerization