Figure 1. Correlations between cAMP, cGMP, and Ca²⁺ in growth cones.

(a) Representative fluorescence image of an Epac1-camps and red cGES-DE5 co-expressing growth cone. Lines drawn as cyan, green, yellow, and orange indicate the cell edge at 0, 20, 40, and 60 min after the onset of image acquisition, respectively. Scale bar represents 10 μm. (b) Spontaneous changes of ΔR/R_average of ECFP/EYFP (cAMP) and T-Sapphire/dimer2 (cGMP) averaged within the ROIs shown in (a). (c) Negative correlation between cAMP and cGMP levels in the growth cones (correlation coefficient is −0.71, 5611 time points from 13 growth cones). (d) Cross correlation function between the spontaneous dynamics of cAMP and cGMP in the growth cones (n = 13) showed a negative correlation without delay. Data are presented as means ± s.e.m. (e) Representative fluorescence image of an Epac1-camps and SapRC2.12 co-expressing growth cone. The colored lines are the same as in (a). Scale bar represents 10 μm. (f) Representative time course changes in spontaneous ΔR/R_average values of ECFP/EYFP (cAMP) and dimer2/T-Sapphire (Ca²⁺) averaged within the ROIs shown in (e). (g) No correlation between cAMP and Ca²⁺ levels in the growth cones (correlation coefficient is −0.19, 8529 time points from 27 growth cones). (h) Heat map showing representative temporal changes in the cross correlation function between the short-term dynamics of cAMP and Ca²⁺ shown in (f) (see Methods).