Fig. 5. Caffeine increased the amplitude of depolarization-evoked Ca²⁺ transients. Caffeine (500 µM in the bathing solution) reversibly increased the amplitude of depolarization-evoked [–70 mV to 10 mV (B)] Ca²⁺ transients (A). The amount of Ca²⁺ entering the cell by depolarization (i.e. the `calculated' increase in [Ca<sup>2+</sup>]<sub>c</sub>) (red line) under control conditions (Di), with caffeine (Dii) and after caffeine washout (Diii) was compared with the `measured' increase in [Ca²⁺]_c (blue line) as determined from the Ca²⁺ transient in the same cell. The time courses of the `measured' and `calculated' Ca²⁺ increases (see Materials and Methods) were similar. There was a greater increase in the `measured' Ca<sup>2+</sup> value for a similar `calculated' Ca²⁺ value in caffeine than in its absence (control). Caffeine removal partially restored the relationship between the `calculated' and `measured' increases in [Ca²⁺]_c. A-D are components of the same experiment. These results show that these concentrations of caffeine cause CICR after depolarization-evoked I_Ca.