Tbx3: a new trick for an 'old' myocyte?

Abstract

This editorial refers to ‘T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells’ by M.L. Bakker et al ., doi:10.1093/cvr/cvs120. Tbx3: a new trick for an ‘old’ myocyte? Well, not quite … Tbx3 is a T-box transcription factor that is expressed in the pacemaking and conduction system myocytes beginning during early embryonic stages of cardiac development.1 When expressed in embryonic atrial chamber myocytes, ectopic induction of spontaneous pacemaking activity in atrial myocardium was observed in vivo , thereby suggesting that Tbx3 can ‘impose’ pacemaking capability upon otherwise unsuspecting working myocytes.2 Bakker et al. 3 test the hypothesis that Tbx3 would also be able to induce pacemaker activity in mature adult cardiac myocytes. Like the proverbial ‘old dog’, however, it appears that it is also difficult to teach old myocytes this new trick. Bakker et al .3 show that while Tbx3 does repress certain genes typically excluded from pacemaking centres such as those encoding the gap junction proteins connexin 40 (Cx40) and connexin 43 (Cx43) in adult mouse atrial myocytes, it failed to induce the pacemaker channel protein encoded by the hyperpolarization-activated cyclic nucleotide-gated 4 ( Hcn4 ) gene. Consequently, no spontaneous sinusoidal action potentials characteristic of those typically observed in sinoatrial node pacemaking myocytes …