cGMPgated

cGMP-gated, also written as cGMP-gated channels or cyclic nucleotide-gated (CNG) channels, are ion channels that open in response to cyclic guanosine monophosphate (cGMP). They are non-selective cation channels permeable to sodium and calcium, and they form functional channels from subunits of the CNGA and CNGB gene families. In vertebrates, these channels are most prominently expressed in sensory neurons, including retinal photoreceptors and olfactory neurons, where they play key roles in signal transduction.

Activation of cGMP-gated channels occurs when cGMP binds to the intracellular cyclic nucleotide-binding domain of the channel. Binding promotes a conformational change that opens the channel pore, allowing cation influx. Calcium entering through these channels provides a negative feedback mechanism via calcium-calmodulin, reducing channel sensitivity and helping adapt the response to sustained stimuli. Ca2+-dependent regulation thus shapes the dynamic range and timing of signaling.

In the retina, cGMP-gated channels are central to the phototransduction cascade. In darkness, high cGMP levels keep the channels open, generating the dark current and depolarizing the photoreceptor. Light activates phosphodiesterase 6, lowering cGMP, leading to channel closure, hyperpolarization, and decreased neurotransmitter release. In olfactory neurons and some other sensory cells, CNG channels participate in transducing odorant or chemical signals through cGMP or cAMP, contributing to sensory perception.

Subunit composition confers functional diversity. Rods typically express CNGA1 and CNGB1, cones express CNGA3 and CNGB3, while olfactory neurons commonly express CNGA2 along with auxiliary subunits. Mutations in CNG channel subunits can cause inherited retinal diseases such as retinitis pigmentosa or achromatopsia, underscoring their physiological importance. Pharmacological modulation and genetic studies of cGMP-gated channels continue to inform understanding of sensory signaling and disease.