HCN4 and atrial fibrillation: At the same time, it has been elucidated that the mRNA and protein expression levels of HCN2 and HCN4 channels increased with age, whereas miR-1 and miR-133 declined with age, implicating elevated HCN activity and reduced miR-1/133-mediated regulation of HCN expression in the pathogenesis of AF [150] (Table 3).