Abstract 18646: Low Metabolic Demand of Induced Pacemaker Cells Enhances Their Survival and Automaticity

The automaticity of cardiac pacemaker cells is central to sinus rhythm generation. As such, metabolism of the pacemaker cells may be optimized to support their survival. However, the scarcity of native sinoatrial node pacemaker cells has impeded gaining insights. We previously demonstrated creation of induced pacemaker cells (iPMs) with singular expression of a transcription factor, TBX18. We hypothesized that the iPMs are similar to native PMs in their mitochondrial architecture, but are distinct from chamber cardiomyocytes in their metabolic signature. The iPMs were created by reprogramming neonatal rat cardiomyocytes (NRVMs) with TBX18. Live-cell, super-resolution imaging illustrated that the mitochondria are smaller and globular in the iPMs and native PMs in contrast to large, tubular networks in chamber cardiomyocytes. This suggested lower Ox-Phos capacity in pacemaker cells relative to chamber cardiomyocytes. Indeed, both basal and maximal oxygen consumption rates were 51±0.3% and 29%±1.4% lower in ...