Sinoatrial node pacemaker cells: cardiomyocyte- or neuron-like cells?

nature of SANPCs remains incompletely known.In general, SANPCs have long been considered as specialized cardiomyocytes (Van Eif et al., 2018;Linscheid et al., 2019;Galang et al., 2020; ).However, SANPCs do not have myofibril and T-tube, thus not sharing the contractility property of cardiomyocytes (Satoh, 2003;Protze et al., 2017).Interestingly, SANPCs share some electrophysiological characteristics with neurons: excitability and conductivity.In addition, SANPCs have their intrinsic autonomic rhythm, while neurons also possess the intrinsic ability to generate spontaneous electrical impulses (Lisman et al., 2018).Whether SANPCs are neuron-like cells that reside in the heart remains enigmatic in the field.In this issue of Protein & Cell, Chen and his colleagues demonstrated that, by single-cell transcriptome analysis, SANPCs co-clustered with neurons of visual cortex.SANPCs expressed cell markers of glutamatergic neurons and contained key elements of glutamatergic neurotransmitter system, including glutamate synthesis pathway, ionotropic glutamate receptors, metabotropic glutamate receptors, and glutamate transporters.Interventions targeting this glutamatergic neurotransmitter system had an extraordinary effect on the spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca 2+ transients frequency in single SANPC.This elegant work reveals for the first time that SANPCs are glutamatergic neuron-like cells in the heart, shedding new light on our understanding of the fundamental biology of SAN.