Ryanodine stores and calcium regulation in the inner segments of salamander rods and cones

Despite the prominent role played by intracellular Ca2+ stores in the regulation of neuronal Ca2+ homeostasis and in invertebrate photoreception, little is known about their contribution to the control of free Ca2+ concentration ([Ca2+](i)) in the inner segments of vertebrate photoreceptors. Previously, caffeine-sensitive intracellular Ca2+ stores were shown to play a role in regulating glutamate release from photoreceptors. To understand the properties of these intracellular stores better we used pharmacological approaches that alter the dynamics of storage and release of Ca2+ from intracellular compartments. Caffeine evoked readily discernible changes in [Ca2+]i in the inner segments of rods, but not cones. Caffeine-evoked Ca2+ responses in cone inner segments were unmasked in the presence of inhibitors of the plasma membrane Ca2+ ATPases (PMCAs) and mitochondrial Ca2+ sequestration. Caffeine-evoked responses were blocked by ryanodine, a selective blocker of Ca2+ release and by cyclopiazonic acid, a blocker of Ca2+ sequestration into the endoplasmic reticulum. These two inhibitors also substantially reduced the amplitude of depolarization-evoked [Ca2+](i) increases, providing evidence for Ca2+-induced Ca2+ release (CICR) in rods and cones. The magnitude and kinetics of caffeine-evoked Ca2+ elevation depended on the basal [Ca2+](i), PMCA activity and on mitochondrial function. These results reveal an intimate interaction between the endoplasmic reticulum, voltage-gated Ca2+ channels, PMCAs and mitochondrial Ca2+ stores in photoreceptor inner segments, and suggest a role for CICR in the regulation of synaptic transmission.