A MODEL FOR CA2+ OSCILLATIONS IN LYMPHOCY TES BASED ON THE REGULATIONOF CA2+ ENTRY INTO THE CELL

Recent experimental data indicate that Ca2+ entry into T-lymphocytes c an be activated by cytosolic Ca2+ via calmodulin. We have constructed a mathematical model which accounts for this activation along with the regulation of Ca2+ entry by the filling state of intracellular Ca2+ s tores. It is shown that the steady state of the model at certain condi tions becomes unstable, and this gives rise to sustained oscillations. The transition from the resting state to oscillations can be evoked b y the activation of stored Ca2+ release as well as the inhibition of i ntracellular Ca2+-ATPase. At a sufficiently high intensity of external stimulation, the response takes the form of a single transient declin ing to an elevated plateau. An increase in the concentration of extrac ellular Ca2+ increases both the amplitude and period of the oscillatio ns, while cessation of Ca2+ entry interrupts the oscillations immediat ely. The form of cytosolic Ca2+ oscillations is characterized by sharp peaks and more smooth changes in the vicinity of the minima situated above the resting level. These properties agree well with the experime ntal observations on single T-lymphocytes. As an experimentally testab le prediction, the influence of cytosolic Ca2+ buffers on calcium resp onses is demonstrated. The results of the model analysis suggest that calcium oscillations in T-lymphocytes may be a consequence of the prop osed dual regulation of Ca2+ entry.