Molecular and functional characterization of the mouse intracardiac nervous system

Abstract

AbstractBackgroundThe intracardiac nervous system (ICNS) refers to clusters of neurons, located within the heart, that participate to the neuronal regulation of cardiac functions and are involved in the initiation of cardiac arrhythmias. Therefore, deciphering the role of the ICNS in cardiac physiology and physiopathology is mandatory. Whereas transgenic mouse models represent powerful tools to reach this goal, the mouse ICNS is still poorly characterized.ObjectiveThe objective of the present study was to provide a phenotypic, electrophysiological and pharmacological characterization of the mouse ICNS.MethodsGlobal cardiac innervation and phenotypic diversity was investigated by performing 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 identified the expression of 7 distinct neuronal markers within mouse intracardiac neurons demonstrating the neurochemical diversity of this network. Of note, we described for the first time in mouse, the existence of neuron expressing the calcium binding protein calbindin, the neuropeptide Y (NPY) and the cocain and amphetamine regulated transcript (CART) peptide. Electrophysiological studies also revealed the existence of two different neuronal population based on their electrical behavior. Finally, we demonstrated that these neurons can be modulated by several neuromodulators.ConclusionThis study demonstrated that mouse ICNS shares similar molecular and functional complexity to that of other species and therefore is a suitable model to decipher the role of individual neuronal subtypes in the modulation of cardiac function and in the initiation of cardiac arrhythmias.