Po-02-241 cardiac sympathetic remodeling and sk channels upregulation, the possible mechanisms of noise exposure associated atrial arrhythmogenesis

Environmental noise exposure may increase sympathetic tone and lead to atrial fibrillation (AF) and mortality. The small conductance Ca2+- activated K+ (SK) channels play important roles in the repolarization of atria. The regulation of SK channels might be involved in modulating cardiac electrophysiology via the autonomic nervous system (ANS). Apamin blocks SK channels specifically and is used for evaluating the roles of SK channels regulation related to noise exposure. To determine how ANS regulates SK channels under noise exposure. We used a noise exposure (NOE) mice model with broad-band noise 20-20k Hz for 28 days to induce atrial myopathy. A total of 12 NOE and 9 control mice were used in the study. Dual optical mapping was performed via Langendorff perfused intact hearts to measure the baseline and post-apamin atrial action potential duration (APD), calcium transient duration (CaTD) and conduction velocity (CV) in the NOE and control mice. The expression of SK channel proteins (SK1-3), tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) was detected by immunohistochemistry. The degree of myocardial fibrosis in the atria was detected by Masson's trichrome staining. Optical mapping study showed no APD difference (26.26±3.69 vs 27.76±2.36 ms, p=0.69) but prolonged CaTD (52.67±1.91 vs 49.65±3.4 ms, p=0.03) in NOE compared with control mice atria at baseline. The ratio of ΔAPD (the difference in the APD after and before apamin) and baseline was higher in NOE than in control mice (0.221±0.231 vs 0.011±0.52, p=0.015), meaning that noise exposure contributed to the upregulation of SK channels. Atrial CV was higher in NOE than in control mice (44.9±4 vs 39.2±3.5 cm/s, p=0.019); after apamin administration, it was significantly lower in NOE than in control mice (30.9±4.8 vs 34.2±3.5 cm/s, p=0.045). IHC study showed SK1-3, TH, GAP43 and trichrome staining were significantly higher in NOE than in control atria (18445.3±2527.9 vs 11228.4±2276.9 μm2/ mm2, 16063.6±1974 vs 9760.17±2576.8 μm2/mm2, 9304.3±633.1 vs 5994.7±1131.8 μm2/ mm2, 1019.9±189.8 vs 622.6±252.3 μm2/ mm2, 733.5±449.1 vs 117.4±53.4 μm2/ mm2, 7449.9±4274.7 vs 492.6±353.9 μm2/ mm2, all p≤0.01). Additionally, AF can be induced in 17% (2/12) of NOE but never in control mice (p=0.14). Noise exposure induces cardiac ANS remodeling, fibrosis and SK currents upregulation. It partially explains the mechanism of noise-induced atrial arrhythmia.