Table 2.

Effect of GIRK1/4 modifications in cardiac physiology.

Modification	Species	Effect in Cardiac Physiology	Reference
GIRK1 gene ablation GIRK4 gene ablation	Mouse	Loss of parasympathetic regulation Loss of heart rate dynamics	[55]
GIRK4 gene disruption	Mouse	IKACh effect in heart rate	[15]
GIRK4 knockout mice	Mouse	Atrial fibrillation	[88]
↑ GIRK4 mRNA in sinoatrial myocytes	Dog	Heart failure	[89]
GIRK blockade	Dog	Suppression of atrial arrythmias	[90]
GIRK genetic variations	Human	Βγ-signaling pathway variations Heart-rate variations	[94]
GIRK4 mutation	Human	Familiar LQTS	[20]
IKACh constitutive activation	Human	Chronic atrial fibrillation	[95,96]
IKACh gradient current	Human	Paroxysmal atrial fibrillation	[97]
GIRK4 overexpression	Human	Protective against adenosine-induced atrial fibrillation	[98]
GIRK4 silencing	Human	Arrhythmia-control mechanism	[99]
GIRK4 gain-of-function	Human	Familial SND	[101]
GIRK overfunction	Human	Atrial fibrillation and SND	[102]

IKACh: muscarinic receptor-activated current; SND: sinus-node dysfunction; LQTS: long QT syndrome augmented.