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bioRxiv · 10.1101/2021.10.15.464492

Molecular and functional characterization of the mouse intracardiac nervous system

Lizot, G.·Pasqualin, C.·Tissot, A.·Pages, S.·Chatelier, A.
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Abstract

BackgroundThe intracardiac nervous system (ICNS) refers to clusters of neurons, located within the heart, which participate to the neuronal regulation of cardiac functions and which are involved in the initiation of cardiac arrhythmias. Therefore, deciphering its role in cardiac physiology and physiopathology is mandatory. ObjectiveThe aim of this study is to provide a phenotypic, electrophysiological and pharmacological characterization of the mouse ICNS, which is still poorly characterized. MethodsGlobal cardiac innervation and phenotypic diversity were investigated using immunohistochemistry on cleared murine heart and on tissue sections. Patch clamp technique was used for electrophysiological and pharmacological characterization of isolated mouse intracardiac neurons. ResultsWe have identified the expression of seven distinct neuronal markers within mouse ICNS, thus proving the neurochemical diversity of this network. Of note, it was the first time that the existence of neurons expressing the calcium binding protein calbindin, the neuropeptide Y (NPY) and the cocain and amphetamine regulated transcript (CART) peptide, was described in the mouse. Electrophysiological studies also revealed the existence of four different neuronal populations based on their electrical behavior. Finally, we showed that these neurons can be modulated by several neuromodulators. ConclusionThis study showed that mouse ICNS presents a molecular and functional complexity similar to other species, and is therefore a suitable model to decipher the role of individual neuronal subtypes regarding the modulation of cardiac function and the initiation of cardiac arrhythmias.

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Lizot, G., Pasqualin, C., Tissot, A., Pages, S., Chatelier, A.. 2021-10-16. Molecular and functional characterization of the mouse intracardiac nervous system. https://doi.org/10.1101/2021.10.15.464492

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