Circular RNA mmu_circ_0005019 regulates small conductance calcium-activated potassium current and action potential duration in mouse cardiomyocytes

To investigate the effect of mmu_circ_0005019 on regulating Kcnn3 expression, small conductance calcium-activated potassium current (I_K,Ca) which is generated by the small conductance calcium-activated potassium (SK) channel that is partly coded by Kcnn3, and action potential duration (APD).

We transfected pcDNA3.1-mmu_circ_0005019 expressing vectors and 2 independent small interfering RNAs into HL-1 cells to establish gain- and loss-of-expression cell models, respectively. The transfected cells were divided into overexpression group(n=3), empty vector group(n=3), interference 1 group(n=3), interference 2 group(n=3), and blank control group(n=3). RT-qPCR and Western blotting were used to determine the expression of Kcnn3. Whole-cell patch clamp technology was performed to record the I_{K, Ca} and APD. The effects of mmu_circ_0005019 on Kcnn3 expression, I_{K, Ca} and APD were observed.

Gain- and loss-of-expression cell models were established successfully. The expression of Kcnn3 and I_K,Ca current density significantly increased, and the APD was shortened in overexpression group compared with empty vector group(P < 0.05). The expression of Kcnn3 and I_K,Ca current density were significantly decreased, and the APD was prolonged in interference groups compared with blank control group(P < 0.05).

Mmu_circ_0005019 promotes the expression of Kcnn3 and its coding channel protein, which regulates IK,Ca and APD in mouse cardiomyocytes, and may play a promoting role in the occurrence of atrial fibrillation.