ASSA13-06-2 Characterization of Small-Conductance Ca2+-Activated K+ Channels in Patients with Chronic Atrial Fibrillation

2013 
Introduction In 2003, Small-Conductance of Ca 2+ -activated K + channels (SK) are first reported to present in Cardiac myocytes, which is expressed more abundant in the atria compared with the ventricles. Genetic knockout of the SK channels results in the delay in cardiac repolarization and showed inducible atrial fibrillation (AF). The purpose of this study was to confirm whether SK channels are involved in electrical remodelling of human chronic atrial fibrillation (CAF). Methods The ionic currents were recorded using whole-cell Conventional patch clamp techniques (35 appendages from patients with SR and 18 appendages from patients with CAF). SK2 channel protein expressions were assayed by western blot technique (12 appendages from patients with SR and 24 preparations from patients with CAF). Results Our result indicate that SK channels present in patients atrial with SR Group and CAF Group, identified it with SK channel blocker apamin (100 nmol/L). SK channels are voltage-independent and inwardly rectifying. The SK channel current densities were significantly increased in CAF (n = 24,[Ca 2+ ] i = 500nmol/L, p 2+ ] i = 500nmol/L). The increased proportion of SK channel current densities in CAF (n = 8, [Ca 2+ ] i = 1000 nmol/L, p 2+ ] i = 1000 nmol/L). it manifested that SK is more sensitive to intracellular Ca 2+ in CAF than in SR. Western bloting result demonstrated that SK2 protein level is significant decrease in CAF than in SR. Conclusion Our results showed SK channels present in patients atrial with SR and CAF; SK channel density in CAF were significantly increase than in SR. In patients with CAF, the SK channels are more sensitive to [Ca 2+ ] i . Compared with SR, the protein level of SK2 was down-regulation in Patients atrial with CAF.these results indicated the increase densities of SK channel in CAF maybe depend on the more sensitive to [Ca 2+ ] i and higher intracellular Calcium level, which lead to increase channels activity, not by the numbers of channels. It might be one of the treatment targets of patients with Atrial Fibrillation, involving in human atrial electric remodelling in CAF.
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