HCN Channel

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are members of the voltage-gated pore loop channel superfamily, and are also related to the cyclic nucleotide-gated (CNG) channels as well as to the voltage-dependent KV10–KV12 channels.HCN channels are activated by intracellular cyclic nucleotides, including guanosine-30,50-cyclic monophosphate (cGMP) and adenosine-30,50 -cyclic monophosphate (cAMP), while the modulation of Ih is similar for both cyclic nucleotides, with the same efficacy at least in mammalians, the apparent affinities of Ih are 10–100 fold higher for cAMP than for cGMP. Hyperpolarization-activated cyclic nucleotide-gated channels are integrated by four subunits that together form a central pore. Each subunit contains a voltage-sensor domain and a pore domain contributing to the central pore. HCN channels are also allosterically regulated by other molecules, such as phosphatidylinositol 4,5-biphosphate, cholesterol, H+, and Cl− ions, and modulated by several post-translational modifications, such as phosphorylation (e.g., Src, mitogen-activated protein serine/threonine kinase [p38-MAPK], protein kinase C [PKC], and Ca2+/calmodulin-dependent protein kinase II)


1.Ramírez D, ey al. Molecules. 2018;23(9):2094. Published 2018 Aug 21.