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Renin-angiotensin system is known to induce the development of atrial fibrillation through atrial structural and electrical remodeling. small conductance calcium-activated potassium channels (SK channels) are close association with development and progression of atrial fibrillation. SK2 is the main subunits of SK channels. However, the effect of Angiotensin II on SK channels remain unknown.
Male rats were subcutaneously infused with AngII 200ng/kg/min using Alzet Osmotic minipumps. After administration for 14 days to measure the mRNA and protein expression levels of SK2 by Western blotting and qRT-PCR. SK2 expression levels were measured by administration with Ang II, Valsartan or PD123319 for 72 hours in neonatal rat myocytes. SK2 was measured under conditions SK2 co-transfected with AT1R or AT2R in HEK293T. SK2 interaction with AT1R or AT2R was detected by CO-IP. SK2 trafficking were measured by flow cytometry in HEK293T.
AngII concentration dependently upregulated SK2 mRNA expression level and SK2 protein expression level in adult rat atrial and neonatal rat atrial myocytes. SK2 exists a close protein-protein interaction with and AT2R in HEK293T cells. AngII increased SK2 expression through AT1R. Angiotensin II induced SK channels trafficking from intracellular to cell-surface membrane expression.
The findings revealed that Ang II increases SK2 expression through AT1R by SK2 trafficking from intracellular to the plasma membrane in atrial myocytes, which involving in electrical remodeling and provides arrhythmic substrate.