Phototransduction & Photoreceptor Physiology

Overview

Phototransduction is the biochemical cascade that converts absorbed light into an electrical signal in rod and cone photoreceptors. It runs on a G-protein coupled receptor, like hormone and neurotransmitter signaling elsewhere in the body, with one feature that runs against intuition: photoreceptors are active and release neurotransmitter continuously in darkness. Light shuts that signal off. Everything else on this page follows from that inversion.

The page follows one photon in order: the resting state in the dark, what light does to it, how the response is switched off, and how the pigment is regenerated. It then compares rods with cones, shows how the ERG reads the pathway, and maps the inherited diseases onto each step.

In the Dark: The Dark Current

In darkness, cyclic GMP (cGMP) binds cGMP-gated cation channels in the outer segment membrane and holds them open. Sodium and calcium flow in steadily. This inward flow is the dark current, and it keeps the photoreceptor depolarized enough to release glutamate continuously onto downstream bipolar cells.

In the Light: The Cascade

A photon sets off five steps:

1. The pigment absorbs the photon. The chromophore 11-cis-retinal, common to rod and cone pigments, isomerizes to all-trans-retinal. That shape change activates the opsin protein. In rods, rhodopsin becomes its signaling form, metarhodopsin II.
2. Rhodopsin activates transducin. It catalyzes GDP-GTP exchange on transducin, a heterotrimeric G-protein.
3. Transducin activates phosphodiesterase (PDE6), which hydrolyzes cGMP.
4. The channels close. As cGMP falls, the cGMP-gated channels close and the dark current stops.
5. The cell hyperpolarizes and glutamate release falls.

Steps 2 and 3 amplify the signal. One activated rhodopsin can activate hundreds of transducin molecules before it is deactivated, and each activated PDE6 hydrolyzes many cGMP molecules per second. One photon can therefore close hundreds of channels, which gives rods their single-photon sensitivity.

Bipolar cells read the fall in glutamate in two opposite ways. ON-bipolar cells express mGluR6, a sign-inverting metabotropic receptor, so falling glutamate depolarizes them. OFF-bipolar cells use ionotropic glutamate receptors and depolarize with rising glutamate instead. This is how one photoreceptor signal splits into parallel ON and OFF pathways.

Switching Off and Adapting

Calcium is the signal that ends the response. Calcium enters only through the open channels, so it is high in the dark and falls in the light. That fall does two things.

It shuts rhodopsin off. In the dark, high calcium keeps the calcium-binding protein recoverin inhibiting rhodopsin kinase. When calcium falls, recoverin releases the kinase, which phosphorylates activated rhodopsin. Arrestin then binds the phosphorylated receptor and blocks further transducin activation.

It rebuilds cGMP. Falling calcium activates guanylate cyclase through guanylate cyclase activating proteins (GCAPs). The new cGMP reopens the channels. Under sustained bright light this is light adaptation: it trims the cell's sensitivity so it does not stay maximally hyperpolarized and unresponsive to further changes in illumination.

Resetting the Pigment: The Visual Cycle

All-trans-retinal, from rods or cones, must be converted back to 11-cis-retinal before the pigment can respond again. This visual cycle takes place in the adjacent retinal pigment epithelium (RPE), not in the photoreceptor. The key enzyme, RPE65 (retinoid isomerohydrolase), converts all-trans-retinyl esters into 11-cis-retinol, which is oxidized to 11-cis-retinal and shuttled back to the outer segment. Phototransduction therefore depends on a healthy RPE.

Rods Versus Cones

Cones run the same steps with their own versions of the proteins (cone transducin, cone PDE6 subunits, cone cGMP-gated channel subunits). These paralogs are structurally similar but genetically distinct, which is why a mutation can knock out rod function, cone function, or both.

Rods are far more sensitive than cones because of their structure. Rod outer segments are longer and packed with stacked discs densely loaded with rhodopsin, which maximizes the chance a photon is absorbed. Cone outer segments have a more folded, less discretely stacked membrane and fewer pigment molecules per cell, and cones are concentrated in the fovea, which handles high-acuity color vision. Hence scotopic vision (rods, dim light) and photopic vision (cones, bright light). It also explains the two phases of dark adaptation: a rapid cone phase, followed by a slower but ultimately far more sensitive rod phase.

Reading the Cascade: Electroretinography

The electroretinogram (ERG) records the retina's summed electrical response to a light flash, and its two main waves come from two consecutive cells. The a-wave is a negative deflection generated by photoreceptor hyperpolarization, the direct signature of channel closure. The b-wave comes primarily from ON-bipolar cell depolarization, one synapse downstream, with a contribution from Müller cells.

So a preserved a-wave with an absent or reduced b-wave, a "negative ERG," means the photoreceptors work but the signal fails at the next synapse. That is the classic finding in congenital stationary night blindness.

Genes Mapped to Each Step

With the sequence in place, the inherited diseases can be read as failures at a specific step:

High-Yield Pearls

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