Regulation of calcium homeostasis in the outer segments of rod and cone photoreceptors

Jun 9, 2018Progress in retinal and eye research

Control of calcium levels in the light-sensing parts of rod and cone cells

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Abstract

Recent evidence suggests a more complex mechanism for calcium extrusion in photoreceptors than previously understood.

Calcium is crucial for the function and survival of rod and cone photoreceptor cells.
Rapid calcium regulation is necessary for phototransduction and light adaptation.
Traditionally, calcium extrusion from rods was thought to occur solely through rod-specific NCKX1, and from cones exclusively via cone-specific NCKX2.
New findings indicate that calcium extrusion in rods may also occur through a NCKX-independent mechanism.
In cones, two distinct NCKX-dependent mechanisms for calcium extrusion have been identified.
Disruption of normal calcium extrusion can lead to functional and structural changes in photoreceptors.

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Calcium plays important roles in the function and survival of rod and cone photoreceptor cells. Rapid regulation of calcium in the outer segments of photoreceptors is required for the modulation of phototransduction that drives the termination of the flash response as well as light adaptation in rods and cones. On a slower time scale, maintaining proper calcium homeostasis is critical for the health and survival of photoreceptors. Decades of work have established that the level of calcium in the outer segments of rods and cones is regulated by a dynamic equilibrium between influx via the transduction cGMP-gated channels and extrusion via rod- and cone-specific Na/Ca, Kexchangers (NCKXs). It had been widely accepted that the only mechanism for extrusion of calcium from rod outer segments is via the rod-specific NCKX1, while extrusion from cone outer segments is driven exclusively by the cone-specific NCKX2. However, recent evidence from mice lacking NCKX1 and NCKX2 have challenged that notion and have revealed a more complex picture, including a NCKX-independent mechanism in rods and two separate NCKX-dependent mechanisms in cones. This review will focus on recent findings on the molecular mechanisms of extrusion of calcium from the outer segments of rod and cone photoreceptors, and the functional and structural changes in photoreceptors when normal extrusion is disrupted. + 2+ +

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Regulation of calcium homeostasis in the outer segments of rod and cone photoreceptors

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