Nkx2.5/CARP signaling pathway contributes to the regulation of ion channel remodeling induced by rapid pacing in rat atrial myocytes.
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.
Department of Cardiovascular Surgery, The Second Affiliated Hospital of Third Military Medical University, Chongqing 400038, P.R. China.
Wei
W
Wang
Department of Cardiovascular Surgery, The Second Affiliated Hospital of Third Military Medical University, Chongqing 400038, P.R. China.
Yun
Y
Zhu
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, P.R. China.
Jianguang
J
Yi
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, P.R. China.
Wei
W
Cheng
D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D000089742:Doublecortin-Like Kinases; D005260:Female; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D000072576:Homeobox Protein Nkx-2.5 / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D000072576:Homeobox Protein Nkx-2.5; C524161:Nkx2-5 protein, rat; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000089742:Doublecortin-Like Kinases; C485526:Dclk1 protein, rat; D017346:Protein Serine-Threonine Kinases