Fig. 3. Model of Ca²⁺-dependent nuclear translocation of NFAT. (A) Schematic illustration of a model of NFAT translocation. NFAT assumes one of the three states, cytoplasmic phosphorylated, cytoplasmic dephosphorylated or nuclear transported. Rate constants are defined as indicated. The dephosphorylation rate constant (k₁) was assumed to be regulated by [Ca²⁺]_i. (B) Model fitting (open circles) to the nuclear translocation time-course of NFAT (continuous trace). Model prediction of the time-course of cytoplasmic-dephosphorylated NFAT is also shown (filled circles). Model para meters used: k₁, 0.359/min (during Ca²⁺ stimulation); k₂, 0.147/min; k₃, 0.060/min; and k₄, 0.035/min. (C) Model prediction of NFAT translocation during Ca²⁺ oscillation. High-frequency Ca²⁺ oscillation maintains dephosphorylated NFAT in the cytoplasm and induces significant nuclear translocation. Low-frequency oscillation results in intermittent dephosphorylation and induces only slight nuclear translocation of NFAT. Model parameters were the same as those used in (B).