In vitro study of the effects of reprogramming neonatal rat fibroblasts transfected with TBX18 on spontaneous beating in neonatal rat cardiomyocytes

Intracardiac injection of the growth-promoting transcription factor of the sinoatrial node T-box18 (TBX18) has been shown to reprogram cardiomyocytes into induced sinoatrial nodes that produce high-frequency and neuroregulated ectopic beats. Fibroblasts, the most important non-cardiomyocyte cell type in the heart, can affect the electrophysiological properties of cardiomyocytes by electrically coupling with them. The aim of the present study was to explore the reprogramming of cardiac fibroblasts (CFs) transfected with TBX18 in vitro and observe its effect on the pacing frequency of neonatal rat ventricular cardiomyocytes (NRVMs) in a co-culture system. CFs transfected with TBX18 could be transformed into cardiac myofibroblasts that expressed high levels of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 protein and low levels of connexin 43 (COX43) and COX45 protein. In addition, TBX18-CFs could increase the beating rates of NRVMs and TBX18-NRVMs in a co-culture system. The results of the present study indicated that the TBX18 gene could induce CFs to undergo a transformation that promotes an increase of the beating rates of NRVMs and TBX18-NRVMs.