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HCN channel blockers act on pacemaker ion channels that open when the cell membrane hyperpolarizes. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels carry the funny current in the sinoatrial node and the related Ih current in neurons. In 1991 cyclic adenosine monophosphate (cAMP) was shown to activate cardiac pacemaker channels directly from the inside of the membrane. The genes were cloned in 1998, and mammals have four isoforms, HCN1 to HCN4. Blockers are used to study heart rate, neuronal excitability, dendritic integration and pain. Ivabradine HCl, zatebradine and cilobradine hydrochloride belong to the bradine group of pore blockers. ZD7288 is widely used in brain slices, and RO-275 and HCN2-IN-3 are aimed at HCN1 and HCN2.
Synonyms: Biphenyl Urea 11
BPU-11 is a HCN4 CLP ligand. It acts by modulating channel function and completely abolishing the cAMP-induced shift in V1/2.
