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Review
. 2002 Sep 1:7:d2023-44.
doi: 10.2741/A896.

Calcium regulation in photoreceptors

David Krizaj  1 , David R Copenhagen
Affiliations
Review

Calcium regulation in photoreceptors

David Krizaj et al. Front Biosci. .

Abstract

In this review we describe some of the remarkable and intricate mechanisms through which the calcium ion (Ca2+) contributes to detection, transduction and synaptic transfer of light stimuli in rod and cone photoreceptors. The function of Ca2+ is highly compartmentalized. In the outer segment, Ca2+ 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, Ca2+ regulates cells' metabolism, glutamate release, cytoskeletal dynamics, gene expression and cell death. We discuss the mechanisms of Ca2+ entry, buffering, sequestration, release from internal stores and Ca2+ extrusion from both outer and inner segments, showing that these two compartments have little in common with respect to Ca2+ homeostasis. We also investigate the various roles played by Ca2+ as an integrator of intracellular signaling pathways, and emphasize the central role played by Ca2+ 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 Ca2+ homeostasis and pathologies leading to retinal dysfunction and blindness.

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Figures

Figure 1
Figure 1
Schematic structure of a rod photoreceptor. The cell is composed of an outer segment which is connected to the inner segment via a thin connecting cilium. The outer segment is filled with disks which contain the visual pigment rhodopsin. The inner segment is composed of an ellipsoid (containing the mitochondria and the endoplasmic reticulum), the cell body and the synaptic terminal. Adapted from (189).
Figure 2
Figure 2
A: Schematic of calcium regulation in the OS. Ca2+ enters the OS through CNG channels and is extruded via NKCX exchangers. [Ca2+]i stimulates guanylyl cyclase (GC) via the GC activating protein (GCAP) and inhibits it via a GC inhibitory protein (GCIP). Ca2+ also inhibits the rhodopsin kinase via its action on recoverin (Rec). Moreover, Ca2+ suppresses further Ca2+ influx via its action on CNG channels, which can be direct, or via calmodulin (CAM). Adapted from (190). B: A topological model of outer segment constituents. Also indicated are retinal diseases linked to mutations in these proteins (See Section 7). ADRP autosomal dominant retinitis pigmentosa; ARRP autosomal recessive retinitis pigmentosa; CSNB congenital stationary night blindness. Adapted from (189).
Figure 3
Figure 3
Signal transmission across the photoreceptor synapse is determined by the properties of voltage-activated Ca2+ current in photoreceptors. A: Voltage-gated Ca2+ current from salamander rod photoreceptor recorded in whole-cell patch configuration. The cell was voltage-clamped at −65 mV and depolarized with a voltage ramp from −70 to + 50 mV. The Ca2+ current activates at around −55 mV and reaches its peak at −10 mV (ref. 21). B: The membrane potential of rod photoreceptors oscillates following removal of Ca2+ channel inactivation. Simultaneous intracellular recording of light responses from a rod and a horizontal cell (HC) in the Xenopus retina. [Ca2+]o was substituted by [Ba2+]o. Under these conditions the rod depolarized by ~5mV and the membrane potential started to oscillate at ~ 3Hz. Note the concomitant change in the waveform of the light response of the horizontal cell (ref. 85).
Figure 4
Figure 4
A: Calcium extrusion is regulated independently in photoreceptor IS (a) and OS (b). Simultaneous [Ca2+]i measurement from salamander rods. a, b: Switch from control saline (2 mM KCl) to high KCl superfusate (90 mM KCl) raised [Ca2+]i in both segments. Immediately following high KCl, the superfusate was switched to saline in which [Na+]o was replaced by [Li+]o (0 mM NaCl, 2 mM KCl, 97 mM LiCl). The IS [Ca2+]i returned to the baseline (panel a), whereas the OS [Ca2+]i remained at a plateau in LiCl saline (panel b). [Ca2+] in the OS returned to baseline following reintroduction of Na+ (20). B: Confocal fluorescence labeling indicates photoreceptor terminals express the isoform 1 of the PMCAs. a: PMCA1 is prominently expressed in photoreceptor synaptic terminals. The labeling is moderate in bipolar cell bodies in the distal INL and weak in horizontal cells. b: Calbindin antibody strongly labels horizontal cells. Prominent somas with dendritic knobs, extending into photoreceptor terminals (arrowheads), are observed. c: Superposition of images from a and b. PMCA1 is expressed in photoreceptor terminals but is excluded from calbindin-immunopositive amacrine cells. Scale bar = 10 μm. d–f: High power fluorescence micrograph of the same section as shown in a–c with magnification focused on the OPL. Each dendritic knob emanating from horizontal cells is associated with exactly one photoreceptor terminal immunolabeled by PMCA1. OPL, outer plexiform layer; INL inner nuclear layer. Scale bar = 2.5 μm. (from 73).
Figure 5
Figure 5
A: Caffeine evokes Ca2+ release from intracellular stores. Two rod photoreceptors were loaded with a Ca2+ indicator dye and depolarized with KCl to raise [Ca2+]i by ~ 300 nM. Exposure to 10 mM caffeine resulted in a complex [Ca2+]i response seen in both cells. The response had two parts: a [Ca2+]i increase followed by a prolonged [Ca2+]i undershoot. Note that in cell 2, a spontaneous [Ca2+]i increase occurred (open arrow) and was also followed by a [Ca2+]i undershoot (arrow). B: A model of calcium store mechanism in rod photoreceptor IS. Ca2+ enters the cell through voltage-gated Ca2+ channels and binds ryanodine receptors localized in the ER, triggering more Ca2+ release. Ca2+, released from the stores, subsequently acts to suppress further Ca2+ influx via an inactivation process. The stores are filled by two separate mechanisms – “sarcoplasmic-endoplasmic reticulum Ca2+ ATPases” (SERCAs) and a “release-activated calcium transport” (RACT) mechanism which may participate in the [Ca2+]i undershoot. The IS also possess IP3-sensitive Ca2+ stores, activated by IP3 and phospholipase C (PLC). The plasma membrane receptors which activate the PLC are still unknown (modified after 21).
Figure 6
Figure 6
A: Relation between voltage and glutamate release from rod photoreceptors. Combined data from two separate experiments. The membrane potential change in a rod evoked by light stimulation and recorded with an intracellular electrode is depicted by the green line. Change in relative glutamate release is depicted by red squares. B: Relation of rod voltage and glutamate release to calcium current. The data points ± SE were obtained from plots in A and fit with a Boltzman function. (modified after 21).
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References

    1. Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 2000;1:11–21. - PubMed
    1. Allbritton NL, Meyer T, Stryer LF. Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate. Science. 1992;258:1812–1815. - PubMed
    1. Nakatani K, Chen C, Koutalos Y. Calcium diffusion coefficient in rod photoreceptor outer segments. Biophys J. 2002;82:728–39. - PMC - PubMed
    1. Bito H, Deisseroth K, Tsien RW. CREB phosphorylation and dephosphorylation: a Ca(2+)- and stimulus duration-dependent switch for hippocampal gene expression. Cell. 1996;27:1203–1214. - PubMed
    1. Juusola M, French AS, Uusitalo RO, Weckstrom M. Information processing by graded-potential transmission through tonically active synapses. Trends Neurosci. 1996;19:292–297. - PubMed

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