Regulation of cardiac CACNB2 by microRNA-499: Potential role in atrial fibrillation

The L-type calcium channel (LTCC) is one of the major ion channels that are known to be associated with the electrical remodeling of atrial fibrillation (AF). In AF, there is significant downregulation of the LTCC, but the underlying mechanism for such downregulation is not clear. We have previously reported that microRNA-499 (miR-499) is significantly upregulated in patients with permanent AF and that KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), is a target of miR-499. We found that CACNB2, an important subunit of the LTCC, is also a target of miR-499. We hypothesize that miR-499 plays an important role in AF electrical remodeling by regulating the expression of CACNB2 and the LTCC. In atrial tissue from patients with permanent AF, CACNB2 was significantly downregulated by 67% (n = 4, p
Highlights • LTCC is downregulated with electrical remodeling of atrial fibrillation. • MiR-499 is increased and CACNB2 is reduced in atria from patients with atrial fibrillation. • MiR-499 binds to the 3′UTR of CACNB2 and inhibits its protein expression. • Downregulation of CACNB2 results in the downregulation of LTCC pore-forming subunit. • MiR-499 contributes to the electrical remodeling of AF through regulation of CACNB2.