Moreover, a familial autosomal recessive POPDC1 mutation has been associated with the phenotype of limb-girdle muscular dystrophy type X2 in combination with AV block [157] and POPDC2 mutations have been shown to cause AV block without a skeletal muscle phenotype [158].The fact that K2P2.1 (TREK-1) channels are activated in acidosis and by mechanical stress has given rise to speculation about a role of this channel in the development of cardiac arrhythmias for more than two decades [28]. This evidence concerns the gene KCNK2 and cardiac rhythm disease.