Pacemaker current

When vagally-released acetylcholine (ACh) binds to muscarinic M2 receptors, this promotes dissociation of βγ subunit complexes, leading to direct opening of the G-protein–gated inwardly rectifying K+ channel (Girk/Kir) IKACh.

[3][8] Because of their relevance to generation of pacemaker activity and modulation of spontaneous frequency, f-channels are natural targets of drugs aimed to pharmacologically control heart rate.

[3] Ivabradine is the most specific and selective If inhibitor and the only member of this family that is now marketed for pharmacological treatment of chronic stable angina in patients with normal sinus rhythm who have a contraindication or intolerance to beta-blockers.

Recent studies have also indicated that funny channel inhibition can be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients with heart rate ≥70 bpm.

Genetic alterations of HCN4 channels (the molecular correlate of sinoatrial f-channels) coupled to rhythm disturbances have been reported in humans.