Hyperpolarization-activated Cyclic Nucleotide-gated Potassium Channel 1

Hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1) is a member of the HCN channel family, which are integral membrane proteins functioning as nonselective voltage-gated cation channels. HCN1 channels contribute to spontaneous rhythmic activity in both cardiac pacemaker cells and neurons, generating an inward current (commonly called "funny current" or If) that plays a crucial role in controlling heart rate and neuronal excitability. The unique feature of these channels is their activation by membrane hyperpolarization rather than depolarization, with their activity further modulated by intracellular cyclic nucleotides such as cAMP. HCN1 expression is prominent in the sinoatrial node, neocortex, hippocampus, cerebellar cortex, dorsal root ganglion, trigeminal ganglion, and brainstem. Mutations in *HCN1* can cause epilepsy. Altered function or expression may also contribute to arrhythmias due to its role in pacemaker currents. Targeting this channel pharmacologically has therapeutic potential for conditions involving abnormal rhythmicity such as atrial fibrillation or certain epilepsies.

Other names

HCN1Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1

Inhibition of HCN1 channel activity.