Ryanodine completely blocks caffeine-induced transient peaks in [Ca²⁺]_i but only partially blocks the caffeine-induced depression of [Ca²⁺]_i. Left, Caffeine (10 mm) elicited the two-phased [Ca²⁺]_i response in a rod constantly depolarized with 20 mm KCl. Middle,Right, Caffeine was reapplied at t = 12 and 30 min after exposure to 50 μm ryanodine. After ryanodine, the first phase of the caffeine-mediated response was irreversibly blocked, and the [Ca²⁺]_iundershoot was reduced to 56 and 44% of control att = 12 and 30 min, respectively.