Key result
Mouse intracardiac nervous system demonstrates distinct neurochemical and electrophysiological neuronal subpopulations.
Why the study?
The intracardiac nervous system regulates cardiac functions and is involved in arrhythmias, but the mouse intracardiac nervous system remains poorly characterized.
The study demonstrates that the mouse intracardiac nervous system possesses a molecular and functional complexity similar to other species, establishing it as a suitable model for studying autonomic modulation in cardiac arrhythmias.
Supports mouse ICNS as arrhythmia model; extends cross-species data but leaves human translation open.
Background The 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. Objective The aim of this study is to provide a phenotypic, electrophysiological and pharmacological characterization of the mouse ICNS, which is still poorly characterized. Methods Global 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. Results We 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. Conclusion This 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 et al. (2021) studied Normal intracardiac nervous system. Physiological observation of the intracardiac nervous system was evaluated on Phenotypic, electrophysiological, and pharmacological characteristics of intracardiac neurons. The mouse intracardiac nervous system exhibits diverse neurochemical markers, including calbindin, NPY, and CART, along with electrophysiologically distinct neuronal populations.
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