In this review we describe some of the remarkable and intricate mechanisms through which the calcium ion (Ca 2+ ) contributes to detection, transduction and synaptic transfer of light stimuli in rod and cone photoreceptors. The function of Ca 2+ is highly compartmentalized. In the outer segment, Ca 2+ controls photoreceptor light adaptation by independently adjusting the gain of phototransduction at several stages in the transduction chain. In the inner segment and synaptic terminal, Ca 2+ regulates cells' metabolism, glutamate release, cytoskeletal dynamics, gene expression and cell death. We discuss the mechanisms of Ca 2+ entry, buffering, sequestration, release from internal stores and Ca 2+ extrusion from both outer and inner segments, showing that these two compartments have little in common with respect to Ca 2+ homeostasis. We also investigate the various roles played by Ca 2+ as an integrator of intracellular signaling pathways, and emphasize the central role played by Ca 2+ as a second messenger in neuromodulation of photoreceptor signaling by extracellular ligands such as dopamine, adenosine and somatostatin. Finally, we review the intimate link between dysfunction in photoreceptor Ca 2+ homeostasis and pathologies leading to retinal dysfunction and blindness.
KeywordsRetina; Photoreceptor; Rod; Cone; Calcium; Plasma Membrane Calcium Atpase; Na-Ca Exchange; Calcium Store; Calcium Buffering; Calcium Channel; Calcium Extrusion; Ryanodine; Inner Segment; Dystrophy; Synaptic Transmission; Review
INTRODUCTIONThe calcium ion (Ca 2+ ) is a major messenger for coordinating activity of eukaryote cells. Its extensive distribution and functioning as a control ion is common to a huge range of eukaryote cell types from animal, plant or fungal sources which diverged billions of years ago. The signaling potential of Ca 2+ is linked to the ability of cells to maintain a large concentration gradient between the cytosol (with basal Ca 2+ levels typically ~ 50 nM) and the extracellular media (with Ca 2+ ~ 1.5 mM). Because of this 10,000-fold difference in [Ca 2+ ]i between the cytosol and the extracellular space, Ca 2+ influx across the plasma membrane and Ca 2+ release from intracellular stores may produce large fluctuations of free cytosolic Ca 2+ (1). Another important feature of Ca 2+ homeostasis is that [Ca 2+ ]i elevations in the cell can be highly localized. We now know that the diffusion of Ca 2+ within the cytosol is much slower than that of other intracellular messengers (2,3). Ca 2+ is thus able to regulate a variety of different functions in different parts of the cell. Such selective action of Ca 2+ is facilitated by Ca 2+ -binding proteins which are often localized to specific sites mediating individual functions (4). To understand Ca 2+ signaling, it is therefore essential to map the spatial distribution of Ca 2+ effector proteins such as Ca 2+ channels, Ca 2+ pumps, cytoplasmic buffers and intracellular Anatomically, primary sensory neurons are notable for their compartmentalization into input ...