Nitric oxide–cGMP–potassium channel signaling pathway

The "Nitric oxide–cGMP–potassium channel signaling pathway" is not a single molecule or receptor, but rather a multi-component biochemical signaling cascade that mediates vasodilation, especially in vascular smooth muscle. The cascade begins with the production of nitric oxide (NO), which activates soluble guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP) levels. cGMP then activates cGMP-dependent protein kinase (PKG), which phosphorylates and activates potassium channels—primarily calcium-activated potassium (KCa) channels, and sometimes ATP-sensitive potassium (KATP) channels—leading to potassium efflux, membrane hyperpolarization, and vascular relaxation[1][2][4][5]. Drugs such as nitrovasodilators and natural compounds like nothofagin exert their effects through this pathway. The pathway is targeted therapeutically in cardiovascular disorders but is not itself a discrete drug target or receptor[1][5]. Additional notes: - **is_incorrect:** This entry refers to a pathway, not an individual druggable target such as a single receptor or channel protein. For structured drug target databases, this should be flagged as "too broad" or "not a single molecular entity." - Primary molecular targets that mediate the key steps in this pathway include: soluble guanylate cyclase (enzyme), cGMP-dependent protein kinase (enzyme), and potassium channels (ion channels, specifically KCa and KATP types)[1][2][4]. - **If a single "target" is required:** Users should annotate the specific potassium channel subtype (e.g., "Big conductance calcium-activated potassium channel alpha subunit (KCNMA1)" or "ATP-sensitive potassium channel subunit (KCNJ11/Kir6.2 or ABCC8/SUR1)") or the upstream enzyme (e.g., "cGMP-dependent protein kinase 1 (PRKG1)").

Other names

Nitric oxide pathwayNO/cGMP/K+ channel pathwayNitric oxide–cGMP–K⁺ channel axis

Activation of cGMP-dependent protein kinase (PKG) Opening of calcium-activated potassium (KCa) channels Direct activation or modification (S-nitrosylation) of potassium channels