In phototransduction by rod photoreceptors, light isomerizes 11-cis-retinal to all-trans-retinal, activating rhodopsin → transducin (Gt) → phosphodiesterase (PDE6) cascade. PDE6 hydrolyzes cGMP, closing CNG channels and hyperpolarizing the rod. Recovery of the dark current requires resynthesis of cGMP. Which enzyme is responsible for cGMP resynthesis and what stimulates it during recovery?

• A Adenylyl cyclase stimulated by Gs to convert ATP to cAMP, which cross-activates cGMP-phosphodiesterase in reverse
• B Photoreceptor-specific phospholipase C that generates IP3, activating IP3R to release Ca²⁺ which activates guanylyl cyclase
• C Retinal guanylyl cyclase (RetGC) stimulated by guanylyl cyclase activating protein (GCAP) when intracellular Ca²⁺ falls during hyperpolarization ✓
• D Rhodopsin kinase regenerates cGMP as a byproduct of rhodopsin phosphorylation and arrestin binding

Explanation

During the light response, CNG channel closure reduces Na⁺ and Ca²⁺ entry; a Ca²⁺-permeable CNG channel carries both ions in the dark. As Ca²⁺ influx stops but Na-Ca-K exchangers continue to extrude Ca²⁺, intracellular Ca²⁺ falls. Low Ca²⁺ activates GCAP (guanylyl cyclase-activating protein 1 and 2) — which at resting dark Ca²⁺ levels is inhibitory on RetGC but at low Ca²⁺ becomes activating. Activated RetGC resynthesizes cGMP, reopening CNG channels and restoring the dark current — this constitutes the Ca²⁺-mediated negative feedback for recovery and light adaptation. Mutations in GCAP and RetGC cause cone-rod dystrophies.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.