The dynamic range and domain-specific signals of intracellular calcium in photoreceptors

Vertebrate photoreceptors consist of strictly delimited subcellular domains: the outer segment, ellipsoid, cell body and synaptic terminal, each hosting crucial cellular functions, including phototransduction, oxidative metabolism, gene expression and transmitter release. We used optical imaging to explore the spatiotemporal dynamics of Ca2+ signaling in non-outer segment regions of rods and cones. Sustained depolarization, designed to emulate photoreceptor activation in the darkness, evoked a standing Ca2+ gradient in tiger salamander photoreceptors with spatially-averaged intracellular Ca2+ concentration within synaptic terminals of ∼2 μM and lower (∼750 nM) intracellular calcium concentration in the ellipsoid. Measurements from axotomized cell bodies and isolated ellipsoids showed that Ca2+ enters the two compartments via both local L-type Ca2+ channels and diffusion. The results from optical imaging studies were supported by immunostaining analysis. L-type voltage-operated Ca2+ channels and plasma membrane Ca2+ ATPases were highly expressed in synaptic terminals with progressively lower expression levels in the cell body and ellipsoid. These results show photoreceptor Ca2+ homeostasis is controlled in a region-specific manner by direct Ca2+ entry and diffusion as well as Ca2+ extrusion. Moreover, quantitative measurement of intracellular calcium concentration levels in different photoreceptor compartments indicates that the dynamic range of Ca2+ signaling in photoreceptors is approximately 40-fold, from ∼50 nM in the light to ∼2 μM in darkness.