Distinct Excitability Properties of Cardiac Calbindin Neurons: Identifying a Unique Neuronal Population
The intrinsic cardiac nervous system is a complex system that plays a critical role in the regulation of cardiac physiological parameters and has been shown to contribute to cardiac arrhythmias. To date, several types of neurons with distinct neurochemical and electrophysiological phenotypes have been identified. However, no study has correlated the neurochemical phenotype to a specific electrophysiological behavior. Calbindin-D28k, a calcium binding protein, is expressed in numerous cardiac neurons. Given that changes in neuronal excitability have been associated with arrhythmia susceptibility and that calbindin expression has been associated with modulations of neuronal excitability, our objective is to assess whether the cardiac calbindin neuronal population has specific properties that could be involved in cardiac modulation and arrhythmias. By using a Cre-Lox mouse model to specifically target calbindin neurons with a fluorescent reporter, we characterized the neurochemical and the electrophysiological phenotype of this cardiac neuronal population. Calbindin neurons exhibit a specific neurochemical profile and a larger soma with shorter neurite length compared to other neurons. This was combined with a distinct electrophysiological signature characterized by a lower excitability with a predominantly phasic profile associated to a lower N-type calcium current density. These properties resemble to the cardiac neuronal remodeling observed in pathologies such as type II diabetes and heart failure. Therefore, we believe that this specific neuronal population deserves investigations in the context of these pathologies.