Nkx2.5/CARP signaling pathway contributes to the regulation of ion channel remodeling induced by rapid pacing in rat atrial myocytes

Abstract

Remodeling of atrial electrophysiology and structure is the primary feature of atrial fibrillation (AF). Evidence suggests that abnormalities in the expression levels of embryological cardiovascular development‑associated transcription factors, including Nkx2.5, are crucial for the development of AF. Rat atrial myocardial cells (AMCs) in culture dishes were placed in an electric field and stimulated. Transmission electron microscopy was used to observe the ultrastucture prior to and following rapid pacing. The action potential durations and effective refractory periods were measured. RT‑PCR and western blotting were performed to investigate the effect of rapid pacing on the expression levels of ion channel and nuclear proteins in AMCs. Nkx2.5 short interfering RNA (siRNA) transfection was performed. Through this in vitro rat AMC culture and rapid pacing model, it was demonstrated that rapid pacing shortened the action potential and downregulated the expression levels of L‑type calcium and potassium channels. Expression levels of Nkx2.5 and cardiac ankyrin repeat protein (CARP) were significantly upregulated by rapid pacing at the mRNA and protein levels. siRNA‑mediated Nkx2.5 silencing attenuated the rapid pacing‑induced downreglation of ion channel levels. These results suggest that the Nkx2.5/CARP signaling pathway contributes to the early electrical remodeling process of AF.

Inhibition of the voltage-gated potassium channel Kv1.5 by hydrogen sulfide attenuates remodeling through S-nitrosylation-mediated signaling

“…Such changes have been demonstrated in vivo, following sustained periods of high frequency activity induced by repetitive stimulation 6 , or following sustained tachycardia 7 or atrial fibrillation 8 (AF). Comparable effects have been demonstrated in vitro, for example, in cultured mouse HL-1 atrial myocytes 9 or rat atrial cells 10 . This epigenetic “remodeling” takes hours or days to develop, and may involve changes in the expression, synthesis, transport, insertion or recycling of channels, their protein subunits and associated regulatory proteins 3 – 5 , 11 .…”