HCN Channels

HCN (hyperpolarization-activated, cyclic nucleotide-gated) channels are members of the cyclic nucleotide-regulated channel family along with cyclic nucleotide-gated (CNG) channels. They are cationic channels that open under hyperpolarization.

Literature (5)
Gene Data

HCN Channel Blockers

Cat. No. Product Name / Activity
6542 Ivabradine hydrochloride
HCN channel blocker; inhibits If pacemaker current
0416 YS-035 hydrochloride
Inhibits pacemaker (If) current and K+ outward currents
2202 Zatebradine hydrochloride
Blocks hyperpolarization-activated current (If)
1000 ZD 7288
Inhibits pacemaker (If) current

HCN (hyperpolarization-activated, cyclic nucleotide-gated) channels are members of the cyclic nucleotide-regulated channel family along with cyclic nucleotide-gated (CNG) channels. Each channel is made up of four subunits, with each subunit comprising six transmembrane α-helical segments, with the S4 segment thought to be the voltage sensor. They are cation permeable channels that open under hyperpolarization. In contrast to most voltage-gated ion channels, they are constitutively open at voltages near the resting membrane potential, so influence neuronal excitability, synaptic potential integration and neurotransmitter release. They are also gated by cyclic nucleotides, cAMP and cGMP, which enhance channel activity. There are four HCN isoforms, HCN1, 2, 3 and 4, which vary in their biophysical properties and in their expression levels across the heart and central nervous system; HCN1 is the fastest activating, while HCN4 is the slowest activating form. The C-terminus of the channel contains a cyclic-nucleotide binding domain where cyclic nucleotides confer their regulation.

The HCN channel current (Ih or If) is found in neurons, cardiac pacemaker cells and photoreceptors. In cardiac pacemaker cells the (If) current is known to control heart rate. HCN4 is the major isoform found in the adult sinoatrial node and in humans HCN4 mutations are associated with idiopathic sinus bradycardia and arrhythmias. In neurons HCN channels set the resting potential and contribute to neuronal pacemaking. Ih is activated following the end of the action potential and depolarizes the cell to initiate the next action potential. They contribute to mechanisms of epilepsy and pain.

External sources of pharmacological information for HCN Channels :

Literature for HCN Channels

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HCN Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
HCN1 Human HCN1 NM_021072 O60741
Mouse Hcn1 NM_010408 NP_034538
Rat Hcn1 NM_053375 Q9JKB0
HCN2 Human HCN2 NM_001194 Q9UL51
Mouse Hcn2 NM_008226 NP_032252
Rat Hcn2 NM_053684 Q9JKA9
HCN3 Human HCN3 NM_020897 Q9P1Z3
Mouse Hcn3 NM_008227 NP_032253
Rat Hcn3 NM_053685 Q9JKA8
HCN4 Human HCN4 NM_005477 Q9Y3Q4
Mouse Hcn4 NM_001081192 NP_001074661
Rat Hcn4 NM_021658 Q9JKA7