A minimal mathematical model to study cytoplasmic Ca2+ kinetics in cells

VIGIL MA; SAFFIOTI NA; RINALDI D; MANGIALAVORI I; ROSSI RC; ROSSI JP; FERREIRA GOMES MS

Virtual

Congreso; Primeras Jornadas Virtuales SAB 2020; 2020

Sociedad Argentina de Biofísica

Calcium (Ca2+) is a critical cofactor and signaling mediator in cells, and the concentration of cytosolic Ca2+ ([Ca2+]cyt) is highly regulated. All cells must maintain a low concentration of [Ca2+]cyt (~100 nM) to maintain viability while using their increase as a versatile signaling pathway. It is mainly controlled through a combination of two closely linked processes: Ca2+ release from the endoplasmic reticulum (ER) and Ca2+ entry across the plasma membrane (PM). Resting cells maintain cytosolic [Ca2+] in the nM range through sarcoplasmic reticulum Ca2+ ATPase (SERCA) and plasma membrane Ca2+ ATPase (PMCA) pumps. Our group has studied the role of PMCA in the removal of calcium under different experimental conditions using fluorescence time-course measurements [1,2,3]. The objective of this work is to obtain a simple model to study the role of PMCA in the removal of calcium from the cells. In a typical experiment, [Ca2+]cyt kinetics shows a transient increase upon the applied stimulus, followed by a slow decrease until a stationary level is reached. To analyze our results, we constructed a minimal mathematical model to describe [Ca2+]cyt kinetics in HEK293T cells. Our model can describe both the reticulum Ca2+ depletion and the Ca2+ influx after Store Operated Channels (SOCs) activation. It showed that the rate of PMCA activation is critical, and it must be slower than the rate of calmodulin activation. On the other hand, it was necessary to consider the effect of calcium buffering in cells to fit the model to the experimental data. In conclusion, we constructed a simple model which will allow us to analyze how PMCA responses in a living cell.