Hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) (HCN1)

Hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) is a key member of the HCN channel family, which mediates the hyperpolarization-activated cation current (Ih), also known as the pacemaker current [3, 13]. Primarily expressed in the brain and the sinoatrial node of the heart, HCN1 is unique among voltage-gated channels for its activation by membrane hyperpolarization rather than depolarization [11, 12]. In the central nervous system, it is essential for regulating resting membrane potential, dendritic integration, and rhythmic neuronal activity, particularly within the hippocampus and neocortex [1, 15]. Mutations in the HCN1 gene are linked to severe neurological conditions, including early infantile epileptic encephalopathy (EIEE24) and other forms of epilepsy [8, 11]. Cannabidiol (CBD) has been identified as a direct stimulator of HCN1, increasing its current independently of traditional cannabinoid receptors [1, 7, 14]. This interaction is believed to play a significant role in CBD's therapeutic profile, particularly its ability to reduce neuronal hyperexcitability in seizure disorders and potentially modulate pain signaling [4, 6].

Other names

BCNG-1HAC-2BCNG1EIEE24GEFSP10DEE24Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1

Cannabidiol acts as a direct stimulator of the HCN1 channel, increasing the hyperpolarization-activated current (Ih) independently of cannabinoid receptors [1, 7, 14].