Mathematical modeling of calcium homeostasis in smooth muscle cells while activity of plasma membrane calcium pump is modulated

摘要

A mathematical model of intracellular calcium homeostasis in smooth muscle cells has been investigated by computer modelling method. The results of calculations showed that for the plasma membrane calcium pump (PMCA) the limiting rate ( VsubmPM/sub ) increasing or the Michaelis constant ( KsubmPM/sub ) decreasing result in a lowering of the Casup2+/sup concentration in cytosol and sarcoplasmic reticulum (SR); the slight VsubmPM/sub decreasing or KsubmPM/sub increasing result in fluent cytosolic Casup2+/sup strengthening due to slow basal influx (SBI) since a massive release of Casup2+/sup from SR does not occur. The further VsubmPM/sub decreasing or KsubmPM/sub increasing stimulate the Casup2+/sup-induced Casup2+/sup release from SR and the system passes into oscillation mode; when the certain low VsubmPM/sub or high KsubmPM/sub level is reached the oscillations of Casup2+/sup concentration in cytosol are stopped, there is only first oscillation after which a new level of cytosolic Casup2+/sup concentration is formed fluently: this level is higher than in the initial basal condition (IBC). Sensitivity of myocytes with the lowering of VsubmPM/sub or increasing KsubmPM/sub to agonist action is rising but sensitivity of myocytes with increasing VsubmPM/sub or decreasing KsubmPM/sub to agonist action is reducing. If the PMCA parameters ( VsubmPM/sub or KsubmPM/sub ) are changed then passive influx of Casup2+/sup in cytosol from extracellular space remains virtually invariable and it is equal to SBI value during the whole process. Initial rate of PMCA in a new equilibrium condition (NEC) is equal virtually to initial rate in IBC: it allows to calculate a new value VsubmPM/sub or KsubmPM/sub from cytosolic Casup2+/sup concentration in NEC.