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

Despite the prominent role played by intracellular Ca 2+ stores in the regulation of neuronal Ca 2+ homeostasis and in invertebrate photoreception, little is known about their contribution to the control of free Ca 2+ concentration ([Ca 2+ ] i ) in the inner segments of vertebrate photoreceptors. Previously, caffeine‐sensitive intracellular Ca 2+ 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 Ca 2+ from intracellular compartments. Caffeine evoked readily discernible changes in [Ca 2+ ] i in the inner segments of rods, but not cones. Caffeine‐evoked Ca 2+ responses in cone inner segments were unmasked in the presence of inhibitors of the plasma membrane Ca 2+ ATPases (PMCAs) and mitochondrial Ca 2+ sequestration. Caffeine‐evoked responses were blocked by ryanodine, a selective blocker of Ca 2+ release and by cyclopiazonic acid, a blocker of Ca 2+ sequestration into the endoplasmic reticulum. These two inhibitors also substantially reduced the amplitude of depolarization‐evoked [Ca 2+ ] i increases, providing evidence for Ca 2+ ‐induced Ca 2+ release (CICR) in rods and cones. The magnitude and kinetics of caffeine‐evoked Ca 2+ elevation depended on the basal [Ca 2+ ] i , PMCA activity and on mitochondrial function. These results reveal an intimate interaction between the endoplasmic reticulum, voltage‐gated Ca 2+ channels, PMCAs and mitochondrial Ca 2+ stores in photoreceptor inner segments, and suggest a role for CICR in the regulation of synaptic transmission.