Upregulated Small-Conductance Calcium-Activated Potassium Currents Contribute to Atrial Arrhythmogenesis in High-Fat Feeding Mice.

BACKGROUND: Metabolic syndrome (MetS) is associated with arrhythmias and cardiovascular mortality. Arrhythmogenesis in MetS results from atrial structural and electrical remodeling.

OBJECTIVE: The small conductance Ca2+-activated K+ (SK) currents modulate atrial repolarization and may influence atrial arrhythmogenicity. This study investigated the regulation of SK current perturbed by a high-fat diet (HFD) to mimic MetS.

METHODS: Thirty mice were divided into two groups that were fed with normal chow (CTL) and HFD for 4 months. Electrocardiography and echocardiography were used to detect cardiac electrical and structure remodeling. Atrial action potential duration (APD) and calcium transient duration (CaTD) were measured by optical mapping of Langendorff-perfused mice hearts. Atrial fibrillation (AF) inducibility and duration were assessed by burst pacing. Whole-cell patch clamp was performed in primarily isolated atrial myocytes for SK currents density.

RESULTS: SK currents density is higher in atrial myocytes from HFD than in CTL mice (p ≤ 0.037). The RNA and protein expression of SK channels are increased in HFD mice (p ≤ 0.041 and p ≤ 0.011, respectively). APD is shortened in HFD compared to CTL (p ≤ 0.015). The shortening of the atrial APD in HFD is reversed by the application of 100 nM apamin (p ≤ 0.043). Compared to CTL, CaTD is greater in HFD atria (p ≤ 0.029). Calcium transient decay (Tau) is significantly higher in HFD than in CTL (p = 0.001). Both APD and CaTD alternans thresholds were higher in HFD (p ≤ 0.043), along with higher inducibility and longer duration of AF in HFD (p ≤ 0.023).

CONCLUSIONS: Upregulation of apamin-sensitive SK currents plays a partial role in the atrial arrhythmogenicity of HFD mice.