Characterization of cardiac pacemaker activity in the primate lemur Microcebus murinus

Abstract Mouse lemur ( Microcebus murinus ) is one of the smallest and more ancestral primates known so far. It is an emerging model of senescence and neurodegeneration, thanks to its genetic proximity to humans compared to rodents. Thus, M. murinus could help to better understand cardiac physiology in humans. Nevertheless, the cardiac physiology of M. murinus is still unknown. We had the opportunity to characterize cardiac activity in mouse lemurs, focusing on the pacemaker activity generation by the Sinoatrial node (SAN). Notably, we recorded cardiac activity in animals, isolated hearts, cardiac tissues and SAN pacemaker myocytes. We showed that the heart rate (HR) of mouse lemurs lays in between that of mice and rats, the rodents of closer size with M. murinus . Conversely, the ventricular depolarization of this lemur is more similar to humans or large mammals rather than small rodents. In the SAN myocytes of M. murinus we recorded three of the main ionic currents involved in the SAN pacemaker activity of vertebrates, I f , I Ca,L and I Ca,T , and the expression of the SAN marker HCN4. In parallel, we characterize skeletal muscle-derived stem cells (MDSCs) from M. murinus . These MDSCs differentiate in vitro in automatic cells showing a pacemaker-like (PML) phenotype. These cells show common features with native SAN myocytes and could be useful to test pharmacological strategies to modulate pacemaker activity. In conclusion, the characterization of M. murinus HR and SAN pacemaker activity, together with the generation of PML cells pave the way for comparative studies of cardiac physiology in primates and pharmacologic tests to handle disease of cardiac automaticity