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Review
. 2017 Feb 1;117(2):523-536.
doi: 10.1152/jn.00585.2016. Epub 2016 Nov 2.

Calcium dynamics and regulation in horizontal cells of the vertebrate retina: lessons from teleosts

Michael W Country  1 , Michael G Jonz  2
Affiliations
Review

Calcium dynamics and regulation in horizontal cells of the vertebrate retina: lessons from teleosts

Michael W Country et al. J Neurophysiol. .

Abstract

Horizontal cells (HCs) are inhibitory interneurons of the vertebrate retina. Unlike typical neurons, HCs are chronically depolarized in the dark, leading to a constant influx of Ca2+ Therefore, mechanisms of Ca2+ homeostasis in HCs must differ from neurons elsewhere in the central nervous system, which undergo excitotoxicity when they are chronically depolarized or stressed with Ca2+ HCs are especially well characterized in teleost fish and have been used to unlock mysteries of the vertebrate retina for over one century. More recently, mammalian models of the retina have been increasingly informative for HC physiology. We draw from both teleost and mammalian models in this review, using a comparative approach to examine what is known about Ca2+ pathways in vertebrate HCs. We begin with a survey of Ca2+-permeable ion channels, exchangers, and pumps and summarize Ca2+ influx and efflux pathways, buffering, and intracellular stores. This includes evidence for Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and N-methyl-d-aspartate receptors and for voltage-gated Ca2+ channels. Special attention is given to interactions between ion channels, to differences among species, and in which subtypes of HCs these channels have been found. We then discuss a number of unresolved issues pertaining to Ca2+ dynamics in HCs, including a potential role for Ca2+ in feedback to photoreceptors, the role for Ca2+-induced Ca2+ release, and the properties and functions of Ca2+-based action potentials. This review aims to highlight the unique Ca2+ dynamics in HCs, as these are inextricably tied to retinal function.

Keywords: calcium; horizontal cell; ion channels; retina; teleost.

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Figures

Fig. 1.
Fig. 1.
Ca2+ pathways and their regulation in teleost horizontal cells. 1: In darkness, glutamate (red circles) is released from photoreceptors and binds onto HC glutamate receptors, allowing Ca2+ influx through Ca2+-permeable AMPARs and NMDARs and leading to depolarization of the plasma membrane. 2: Depolarization also opens VGCCs, including L-type and (at least in bass) T-type VGCCs. 3: Glutamate receptors acidify the cytosol, downregulating L-type VGCCs. In contrast, group I and/or III metabotropic glutamate receptors may upregulate VGCCs (see text). 4: Additionally, glutamate triggers CICR from RyRs, further downregulating L-type VGCCs. 5 and 6: The SERCA pump then refills Ca2+ stores, along with SOCs and/or NCXs functioning in reverse. 7: IP3Rs have been found in catfish but do not contribute to CICR. 8: Gap junctions and hemichannels might allow Ca2+ flow between coupled cells or with the extracellular environment in some conditions. 9: Ca2+ influx from AMPARs, NMDARs, and VGCCs is extruded by the NCX and possibly to a lesser extent, the PMCA. 10: Cytosolic Ca2+ is strongly buffered by Ca2+-binding proteins. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; NMDAR, N-methyl-d-aspartate receptor; VGCC, voltage-gated Ca2+ channel; CICR, Ca2+-induced Ca2+ release; RyR, ryanodine receptor; SERCA, sarcoplasmic/endoplasmic reticulum Ca2+ ATPase; SOC, store-operated channel; IP3R, inositol triphosphate receptor; NCX, Na+/Ca2+ exchanger; PMCA, plasma membrane Ca2+-ATPase.
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