title: Ryanodine stores and calcium regulation in the inner segments of salamander rods and cones.
abstract: 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.
authors.affiliation: Department of Ophthalmology, UCSF School of Medicine, San Francisco, CA 94143, USA. krizaj@phy.ucsf.edu
authors.forename: David
authors.initials: D
authors.lastname: Krizaj
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Lai
authors.forename: David R
authors.initials: DR
authors.lastname: Copenhagen
mesh_terms: D000557:Ambystoma / Q000502:physiology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D012433:Ryanodine / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D010726:Phosphodiesterase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium