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

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 Ca Therefore, mechanisms of Ca homeostasis in HCs must differ from neurons elsewhere in the central nervous system, which undergo excitotoxicity when they are chronically depolarized or stressed with Ca 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 Ca pathways in vertebrate HCs. We begin with a survey of Ca-permeable ion channels, exchangers, and pumps and summarize Ca influx and efflux pathways, buffering, and intracellular stores. This includes evidence for Ca-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and N-methyl-d-aspartate receptors and for voltage-gated Ca 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 Ca dynamics in HCs, including a potential role for Ca in feedback to photoreceptors, the role for Ca-induced Ca release, and the properties and functions of Ca-based action potentials. This review aims to highlight the unique Ca dynamics in HCs, as these are inextricably tied to retinal function.