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Schematic model of HCN3 modulation by cholesterol/CHS and cAMP.A, in the absence of ligands or in the presence of inhibitory molecules, cholesterol/CHS binds to the S4-S5 linker and inhibits the opening of the channel. B, in the activation state induced by membrane hyperpolarization and possibly more potent agonists, the channel is open. HCN, Hyperpolarization-Activated Cyclic Nucleotide-gated; CHS, cholesteryl hemisuccinate.
