LF129 11: Sight and Blue Tinged vision (Mechanism)

Receptors with intrinsic enzyme activity: Enzymes are part of the receptor complex itself.
Receptors linked to protein kinases: Activate protein kinases to initiate signaling.
G-protein-coupled receptors (GPCRs): Receptors that transmit signals via G proteins.
Intracellular receptors: Engage with ligands that can cross the membrane to affect gene expression.
Ion channel receptors: Receptors that form ion channels in the membrane, allowing ions to flow when activated.

Light signal travels through neural layers and acts on rods and cones in the outer segment of the retina's photoreceptive membrane.
Photoreceptor cells: Rods specialize in low light vision, while cones are responsible for color vision in bright light.

Comprise inner and outer segments with a primary cilium that plays a role in signaling.
Rod cells have approximately 1000 discs filled with rhodopsin molecules, which are not connected to the plasma membrane.

Rhodopsin: Visual pigment made of opsin (GPCR protein) and 11-cis-retinal (chromophore).
Cis-trans isomerization: Light absorption by 11-cis-retinal causes conformational change; results in activation of rhodopsin (metarhodopsin II).
Moves the side chain of K296, leading to activation of downstream signaling.

Upon light absorption, metarhodopsin II activates the G protein transducin (Gt), facilitating signal transduction through the retinal cells.

Mammalian cells contain various Gα, Gβ, and Gγ proteins used in signal transduction; they activate different pathways.
Gs: Stimulates adenylate cyclase
Gi: Inhibits adenylate cyclase
Gt: Activates cGMP phosphodiesterase
Gq: Stimulates phospholipase C
G12: Activates ion channels.

Transducin (Gt) comprises Gαt, Gβt, and Gγt; Gαt activates cGMP phosphodiesterase to reduce cGMP levels.
Light-induced closure of cGMP-gated ion channels alters the membrane potential in rod cells by reducing the influx of cations, leading to cell hyperpolarization.

Rhodopsin can detect a single photon, enabling rods to respond effectively to very low light intensities.
Under bright light, rods become less sensitive due to the closure of cGMP-gated channels and reduction of intracellular calcium levels.
Re-sensitization: Ca2+ concentration allows guanylate cyclase to regenerate cGMP, reopening ion channels.

1) Prolonged closure of cGMP-gated channels
2) Increased phosphorylation of opsin reduces transducin's activation
3) Arrestin binds to phosphorylated opsin, preventing further activation of transducin.
This process requires time for rods to reset when transitioning from bright to dark environments.

Light exposure causes conversion of light energy into atomic motion via retinal isomerization.
Each metarhodopsin II activates around 500 transducins, leading to significant amplification of the signal (up to 10 million Na+ ion channels are affected).

We are typically trichromats with three types of cone cells (S, M, L) sensitive to blue, green, and red wavelengths respectively.
Peak absorbences: 414-426 nm (blue), 530-532 nm (green), 560-563 nm (yellow-green).
Humans, being trichromats, have selective pressure mechanisms that impact visual pigment sensitivities.

Birds exhibit tetrachromacy; some can see ultraviolet light, while many fish have multiple pigments (pentachromatic).
The evolution of color vision may relate to mate selection in certain species [e.g. peafowl].

Some color-blind individuals may see through camouflage due to their distinct vision processing, favoring their survival in certain contexts.
Examples illustrate that dichromats might have advantages in specific tasks like detecting camouflaged objects.

Sildenafil citrate: A drug that inhibits cGMP phosphodiesterase; can lead to visual side effects like blue-tinged vision by affecting the same pathways utilized in retinal phototransduction.