Phototransduction

In the dark, cGMP levels are high and keep cyclic nucleotide-gated (CNG) channels in the outer-segment membrane open. Na⁺ and Ca²⁺ flow in (the dark current) while K⁺ leaves the inner segment and the Na⁺/K⁺-ATPase restores gradients. The cell sits at ≈−40 mV and releases glutamate continuously.

In light: (1) a photon isomerises 11-cis-retinal → all-trans-retinal — the only light-dependent step; (2) rhodopsin passes through intermediates to metarhodopsin II (R); (3) one R activates hundreds of molecules of the G protein transducin (Gt), exchanging GDP for GTP; (4) Gtα-GTP activates phosphodiesterase 6 (PDE6), each of which hydrolyses thousands of cGMP molecules per second; (5) falling cGMP closes CNG channels; (6) the cell hyperpolarises (towards ≈−70 mV) and glutamate release falls. The cascade's amplification allows a rod to signal a single photon. Paradoxically, light therefore reduces photoreceptor transmitter output: ON bipolar cells (mGluR6, sign-inverting) depolarise and OFF bipolars hyperpolarise.

Recovery and adaptation: rhodopsin kinase (GRK1) phosphorylates R* and arrestin caps it; RGS9 accelerates transducin's GTPase. Because channels are closed, Ca²⁺ influx stops while the Na⁺/Ca²⁺-K⁺ exchanger keeps extruding it; low Ca²⁺ activates guanylate cyclase-activating proteins (GCAPs), which speed cGMP synthesis — the main mechanism of light adaptation. The bleached chromophore (all-trans-retinal → retinol) is shuttled to the RPE, re-isomerised by RPE65 and returned as 11-cis-retinal (the visual cycle); cones also use a Müller-cell pathway, which is why they dark-adapt faster.