Cardiac acetylcholine-gated potassium channel (IK_ACh channel, or Kir3.1/Kir3.4 complex (not universally standardized; see aliases))

The **cardiac acetylcholine-gated potassium channel** is a heterotetrameric inward rectifier potassium channel primarily composed of Kir3.1 (KCNJ3) and Kir3.4 (KCNJ5) subunits, found predominantly in cardiac atrial and pacemaker cells. It is activated by acetylcholine released from parasympathetic nerve endings; acetylcholine binds to the M2 muscarinic receptor, causing G-protein activation and gating of the channel, resulting in outward potassium flow. This channel is central to parasympathetic regulation of heart rate: its activation shortens action potential duration, hyperpolarizes cardiac cells, and slows atrial and nodal conduction. Dysfunction or abnormal regulation of this channel is implicated in arrhythmias, especially atrial fibrillation and bradyarrhythmias[2]. As a proven component in atrial electrophysiology with a clear disease association, it is an established therapeutic target and a subject of ongoing drug discovery for atrial-selective antiarrhythmics[2].

Other names

Acetylcholine-activated potassium channelMuscarinic potassium channelGIRK1/GIRK4 channelInward rectifier potassium channel 3.1/3.4Kir3.1/Kir3.4 channelI_K,ACh (current produced by this channel)KCNJ3/KCNJ5 (genes encoding protein subunits)

Channel opening is mediated by acetylcholine binding to cardiac muscarinic (M2) receptors, leading to G-protein beta/gamma subunit activation of the channel and increased potassium efflux, causing hyperpolarization and slowing heart rate[2]. - Drug antagonists (anticholinergics, antiarrhythmics, investigational small molecules) block this cascade or directly inhibit channel opening.