G protein-gated inwardly rectifying potassium channel (IKACh) (IKACh)

The G protein-gated inwardly rectifying potassium channel (IKACh) is a cardiac potassium channel that mediates the acetylcholine-sensitive K+ current in atrial and nodal myocytes. It is a heterotetrameric structure typically composed of Kir3.1 (GIRK1) and Kir3.4 (GIRK4) subunits, and is activated by direct binding of Gβγ subunits from muscarinic M2 receptor–coupled G-proteins in response to parasympathetic stimulation. IKACh activation increases potassium permeability, causing membrane hyperpolarization and shortening of the cardiac action potential, especially in the atria, thereby slowing the heart rate and facilitating vagal control of cardiac rhythm. IKACh is implicated in multiple cardiac pathologies, especially arrhythmias such as atrial fibrillation, and is a validated drug target for modulating cardiac electrical behavior.

Other names

Acetylcholine-activated potassium channelMuscarinic-gated atrial potassium channelGIRK1/GIRK4 channel (Kir3.1/Kir3.4 channel)G protein-coupled inward rectifier potassium channelAcetylcholine-sensitive K+ current channel

Blockage of IKACh: increases heart rate, used in bradycardia or to terminate vagal-induced arrhythmias; Activation of IKACh: slows heart rate via hyperpolarization and shortening of action potential duration