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Visual phototransduction is the sensory transduction process of the visual system by which light is detected by photoreceptor cells (rods and cones) in the vertebrate retina. A photon is absorbed by a retinal chromophore (each bound to an opsin), which initiates a signal cascade through several intermediate cells, then through the retinal ganglion cells (RGCs) comprising the optic nerve.

Light enters the eye, passes through the optical media, then the inner neural layers of the retina before finally reaching the photoreceptor cells in the outer layer of the retina. The light may be absorbed by a chromophore bound to an opsin, which photoisomerizes the chromophore, initiating both the visual cycle, which "resets" the chromophore, and the phototransduction cascade, which transmits the visual signal to the brain. The cascade begins with graded polarisation (an analog signal) of the excited photoreceptor cell, as its membrane potential increases from a resting potential of -70 mV, proportional to the light intensity. At rest, the photoreceptor cells are continually releasing glutamate at the synaptic terminal to maintain the potential.^[1] The transmitter release rate is lowered (hyperpolarization) as light intensity increases. Each synaptic terminal makes up to 500 contacts with horizontal cells and bipolar cells.^[1] These intermediate cells (along with amacrine cells) perform comparisons of photoreceptor signals within a receptive field, but their precise functionalities are not well understood. The signal remains as a graded polarization in all cells until it reaches the RGCs, where it is converted to an action potential and transmitted to the brain.^[1]

The photoreceptor cells involved in vertebrate vision are the rods, the cones, and the photosensitive ganglion cells (ipRGCs). These cells contain a chromophore (11-cis-retinal, the aldehyde of vitamin A1 and light-absorbing portion) that is bound to a cell membrane protein, opsin. Rods are responsible for vision under low light intensity and contrast detections. Because they all have the same response across frequencies, no color information can be deduced from the rods only, as in low light conditions for example. Cones, on the other hand, are of different kinds with different frequency response, such that color can be perceived through comparison of the outputs of different kinds of cones. Each cone type responds best to certain wavelengths, or colors, of light because each type has a slightly different opsin. The three types of cones are L-cones, M-cones and S-cones that respond optimally to long wavelengths (reddish color), medium wavelengths (greenish color), and short wavelengths (bluish color) respectively. Humans have trichromatic photopic vision consisting of three opponent process channels that enable color vision.^[2] Rod photoreceptors are the most common cell type in the retina and develop quite late. Most cells become postmitotic before birth, but differentiation occurs after birth. In the first week after birth, cells mature and the eye becomes fully functional at the time of opening. The visual pigment rhodopsin (rho) is the first known sign of differentiation in rods. ^[3]

To understand the photoreceptor's behavior to light intensities, it is necessary to understand the roles of different currents.

There is an ongoing outward potassium current through nongated K⁺-selective channels. This outward current tends to hyperpolarize the photoreceptor at around −70 mV (the equilibrium potential for K⁺).

There is also an inward sodium current carried by cGMP-gated sodium channels. This "dark current" depolarizes the cell to around −40 mV. This is significantly more depolarized than most other neurons.

A high density of Na⁺-K⁺ pumps enables the photoreceptor to maintain a steady intracellular concentration of Na⁺ and K⁺.

When light intensity increases, the potential of the membrane decreases (hyperpolarization). Because as the intensity increases, the release of the stimulating neurotransmitter glutamate of the photoreceptors is reduced. When light intensity decreases, that is, in the dark environment, glutamate release by photoreceptors increases. This increases the membrane potential and produces membrane depolarization.^[1]

Photoreceptor cells are unusual cells in that they depolarize in response to absence of stimuli or scotopic conditions (darkness). In photopic conditions (light), photoreceptors hyperpolarize to a potential of −60 mV.

In the dark, cGMP levels are high and keep cGMP-gated sodium channels open allowing a steady inward current, called the dark current. This dark current keeps the cell depolarized at about −40 mV, leading to glutamate release which inhibits excitation of neurons.

The depolarization of the cell membrane in scotopic conditions opens voltage-gated calcium channels. An increased intracellular concentration of Ca²⁺ causes vesicles containing glutamate, a neurotransmitter, to merge with the cell membrane, therefore releasing glutamate into the synaptic cleft, an area between the end of one cell and the beginning of another neuron. Glutamate, though usually excitatory, functions here as an inhibitory neurotransmitter.

In the cone pathway, glutamate:

• Hyperpolarizes on-center bipolar cells. Glutamate that is released from the photoreceptors in the dark binds to metabotropic glutamate receptors (mGluR6), which, through a G-protein coupling mechanism, causes non-specific cation channels in the cells to close, thus hyperpolarizing the bipolar cell.
• Depolarizes off-center bipolar cells. Binding of glutamate to ionotropic glutamate receptors results in an inward cation current that depolarizes the bipolar cell.

In summary: Light closes cGMP-gated sodium channels, reducing the influx of both Na⁺ and Ca²⁺ ions. Stopping the influx of Na⁺ ions effectively switches off the dark current. Reducing this dark current causes the photoreceptor to hyperpolarise, which reduces glutamate release which thus reduces the inhibition of retinal nerves, leading to excitation of these nerves. This reduced Ca²⁺ influx during phototransduction enables deactivation and recovery from phototransduction, as discussed below in § Deactivation of the phototransduction cascade.

1. A photon interacts with a retinal molecule in an opsin complex in a photoreceptor cell. The retinal undergoes isomerisation, changing from the 11-cis-retinal to the all-trans-retinal configuration.
2. Opsin therefore undergoes a conformational change to metarhodopsin II.
3. Metarhodopsin II activates a G protein known as transducin. This causes transducin to dissociate from its bound GDP, and bind GTP; then the alpha subunit of transducin dissociates from the beta and gamma subunits, with the GTP still bound to the alpha subunit.
4. The alpha subunit-GTP complex activates phosphodiesterase, also known as PDE6. It binds to one of two regulatory subunits of PDE (which itself is a tetramer) and stimulates its activity.
5. PDE hydrolyzes cGMP, forming GMP. This lowers the intracellular concentration of cGMP and therefore the sodium channels close.^[5]
6. Closure of the sodium channels causes hyperpolarization of the cell due to the ongoing efflux of potassium ions.
7. Hyperpolarization of the cell causes voltage-gated calcium channels to close.
8. As the calcium level in the photoreceptor cell drops, the amount of the neurotransmitter glutamate that is released by the cell also drops. This is because calcium is required for the glutamate-containing vesicles to fuse with cell membrane and release their contents (see SNARE proteins).
9. A decrease in the amount of glutamate released by the photoreceptors causes depolarization of on-center bipolar cells (rod and cone On bipolar cells) and hyperpolarization of cone off-center bipolar cells.

In light, low cGMP levels close Na⁺ and Ca²⁺ channels, reducing intracellular Na⁺ and Ca²⁺. During recovery (dark adaptation), the low Ca²⁺ levels induce recovery (termination of the phototransduction cascade), as follows:

1. Low intracellular Ca²⁺ causes Ca²⁺ to dissociate from guanylate cyclase activating protein (GCAP). The liberated GCAP ultimately restores depleted cGMP levels, which re-opens the cGMP-gated cation channels (restoring dark current).
2. Low intracellular Ca²⁺ causes Ca²⁺ to dissociate from GTPase-activating protein (GAP), also known as regulator of G protein signaling. The liberated GAP deactivates transducin, terminating the phototransduction cascade (restoring dark current).
3. Low intracellular Ca²⁺ makes intracellular Ca-recoverin-RK dissociate into Ca²⁺ and recoverin and rhodopsin kinase (RK). The liberated RK then phosphorylates the Metarhodopsin II, reducing its binding affinity for transducin. Arrestin then completely deactivates the phosphorylated-metarhodopsin II, terminating the phototransduction cascade (restoring dark current).
4. Low intracellular Ca²⁺ make the Ca²⁺/calmodulin complex within the cGMP-gated cation channels more sensitive to low cGMP levels (thereby, keeping the cGMP-gated cation channel open even at low cGMP levels, restoring dark current)^[6]

In more detail:

GTPase Accelerating Protein (GAP) of RGS (regulators of G protein signaling) interacts with the alpha subunit of transducin, and causes it to hydrolyse its bound GTP to GDP, and thus halts the action of phosphodiesterase, stopping the transformation of cGMP to GMP. This deactivation step of the phototransduction cascade (the deactivation of the G protein transducer) was found to be the rate limiting step in the deactivation of the phototransduction cascade.^[7]

In other words: Guanylate Cyclase Activating Protein (GCAP) is a calcium binding protein, and as the calcium levels in the cell have decreased, GCAP dissociates from its bound calcium ions, and interacts with Guanylate Cyclase, activating it. Guanylate Cyclase then proceeds to transform GTP to cGMP, replenishing the cell's cGMP levels and thus reopening the sodium channels that were closed during phototransduction.

Finally, Metarhodopsin II is deactivated. Recoverin, another calcium binding protein, is normally bound to Rhodopsin Kinase when calcium is present. When the calcium levels fall during phototransduction, the calcium dissociates from recoverin, and rhodopsin kinase is released and phosphorylates metarhodopsin II, which decreases its affinity for transducin. Finally, arrestin, another protein, binds the phosphorylated metarhodopsin II, completely deactivating it. Thus, finally, phototransduction is deactivated, and the dark current and glutamate release is restored. It is this pathway, where Metarhodopsin II is phosphorylated and bound to arrestin and thus deactivated, which is thought to be responsible for the S2 component of dark adaptation. The S2 component represents a linear section of the dark adaptation function present at the beginning of dark adaptation for all bleaching intensities.

The visual cycle occurs via G-protein coupled receptors called retinylidene proteins which consists of a visual opsin and a chromophore 11-cis-retinal. The 11-cis-retinal is covalently linked to the opsin receptor via Schiff base. When it absorbs a photon, 11-cis-retinal undergoes photoisomerization to all-trans-retinal, which changes the conformation of the opsin GPCR leading to signal transduction cascades which causes closure of cyclic GMP-gated cation channel, and hyperpolarization of the photoreceptor cell. Following photoisomerization, all-trans-retinal is released from the opsin protein and reduced to all-trans-retinol, which travels to the retinal pigment epithelium to be "recharged". It is first esterified by lecithin retinol acyltransferase (LRAT) and then converted to 11-cis-retinol by the isomerohydrolase RPE65. The isomerase activity of RPE65 has been shown; it is uncertain whether it also acts as the hydrolase.^[8] Finally, it is oxidized to 11-cis-retinal before traveling back to the photoreceptor cell outer segment where it is again conjugated to an opsin to form new, functional visual pigment (retinylidene protein), namely photopsin or rhodopsin.

Visual phototransduction in invertebrates like the fruit fly differs from that of vertebrates, described up to now. The primary basis of invertebrate phototransduction is the PI(4,5)P₂ cycle. Here, light induces the conformational change into rhodopsin and converts it into meta-rhodopsin. This helps in dissociation of G-protein complex. Alpha sub-unit of this complex activates the PLC enzyme (PLC-beta) which hydrolyze the PIP2 into DAG. This hydrolysis leads to opening of TRP channels and influx of calcium.^{[citation needed]}

Invertebrate photoreceptor cells differ morphologically and physiologically from their vertebrate counterparts. Visual stimulation in vertebrates causes a hyperpolarization (weakening) of the photoreceptor membrane potential, whereas invertebrates experience a depolarization with light intensity. Single-photon events produced under identical conditions in invertebrates differ from vertebrates in time course and size. Likewise, multi-photon events are longer than single-photon responses in invertebrates. However, in vertebrates, the multi-photon response is similar to the single-photon response. Both phyla have light adaptation and single-photon events are smaller and faster. Calcium plays an important role in this adaptation. Light adaptation in vertebrates is primarily attributable to calcium feedback, but in invertebrates cyclic AMP is another control on dark adaptation.^{[9][verification needed]}

• Visual pigments and visual transduction at med.utah.edu
• Transduction of Light Prezi
• A General Overview on Visual Perception at brynmawr.edu
• Phototransduction at the U.S. National Library of Medicine Medical Subject Headings (MeSH)