Mouse lemur, a new animal model to investigate cardiac pacemaker activity in primates
| Autor: | Mattia L. DiFrancesco, Romain Davaze, Eleonora Torre, Pietro Mesirca, Manon Marrot, Corinne Lautier, Pascaline Fontes, Joёl Cuoq, Anne Fernandez, Ned Lamb, Fabien Pifferi, Nadine Mestre-Francés, Matteo E. Mangoni, Angelo G. Torrente |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Microcebus murinus biology Mouse lemur Sinoatrial node medicine.medical_treatment Lemur 030204 cardiovascular system & hematology biology.organism_classification Cardiac pacemaker Cardiovascular physiology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure biology.animal medicine Myocyte Primate Neuroscience 030304 developmental biology |
| Popis: | BackgroundGray mouse lemurs (Microcebus murinus) are the smallest and most ancestral primates known. Their size falls in between that of mice and rats, and their genetic proximity to humans makes them an emerging model to study age-related neurodegeneration. Since mouse lemurs replicate similar senescence processes of humans, they constitute a useful model for studying cardiovascular dysfunctions. However, their cardiac physiology is unknown. Thus, we investigated the cardiac pacemaker activity generated by the sinoatrial node (SAN) of mouse lemurs, presenting the first characterization of heart automaticity in nonhuman primates.Methods and ResultsWe recorded cardiac automaticity in mouse lemurs and in their SAN tissues and pacemaker myocytes. Mouse lemurs have a heart rate (HR) in between those of mice and rats and a similar generation of the SAN electrical impulse. Their SAN myocytes express the main pacemaker currents at densities similar to mice: the hyperpolarization-activated current (If) and the L-type (Ica,L) and T-type (Ica,T) calcium currents. Conversely, their ventricular depolarization resembles that of large mammals and despite the small size of mouse lemurs, the total number of heartbeats in their life corresponds to what can be attained by humans.Using muscle-derived stem cells (MDSCs) from mouse lemurs, we also differentiated pacemaker-like (PML) cells showing spontaneous automaticity and expressing markers of native SAN myocytes (HCN4 and connexin-45).ConclusionsOur characterization of heart automaticity in Microcebus murinus provides new opportunities for comparative cardio-physiology studies in primates and with humans and for testing molecules that could modulate age-related dysfunctions of heart rate. |
| Databáze: | OpenAIRE |
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