Contribution of miRNAs to ion-channel remodelling in atrial fibrillation

Figure 1 Mechanisms of atrial fibrillation. Cytotoxic overloading of Ca²⁺ occurs by a rapid atrial rate. As a result, this acts as a mechanism of cell protection via the inactivation of L-type Ca²⁺ current (I_Ca-L), which in turn reduces the action potential duration (APD) and this consequently shortens the refractory period (RP). This overloading of Ca²⁺ also contributes to an abnormal function of ryanodine receptor channels (RyRs) and intensifies the inward Na⁺-Ca²⁺-exchange current (I_NCX), leading to delayed afterpolarizations (DADs) and ectopic activity. In addition, AF produces hyperpolarization due to increased I_Ca-L, which increases the inward rectifier current (I_K1) and acetylcholine-regulated K⁺ current (I_K-Ach). This also reduces APD and promotes conduction by decreasing of connexin-40 (Cx40).

Figure 2 Mechanisms of electrical remodelling in atrial fibrillation regulated by microRNAs. I_Na: Inward sodium current; I_K1: Inward rectified K⁺ current; I_to: Transient outward potassium currents; I_Ca-L: Inactivation of L-type Ca²⁺ current; I_Kur: Ultrarapid delayed rectifier K⁺ channel; I_Ks: Slow delayed rectifier potassium channel; I_K-Ach: Acetylcholine-activated inward-rectifing potassium channel; I_NCX: Inward Na⁺-Ca²⁺-exchange current; SK3: Small conductance calcium-activated potassium channel 3; I_f: Funny current.