Finding a new job: glutamate signaling acts in atrial cardiomyocytes

Cardiomyocytes (CMs) and neurons possess similar fundamental functions of excitability and conduction.Xie et al. provide evidence that the glutamatergic transmitter system regulating excitability and conduction in neurons is endogenously expressed and active in atrial CMs, uncovering new neuron-like signaling properties of atrial CMs.Cardiac excitability and conduction are fundamental functions of the heart.Regulation of these functions is undeniably complex and involves multiple mechanisms including, but not limited to, autonomic nervous, nitric oxide signaling and redox balance systems.The role of the adrenergic and cholinergic nerves, part of the autonomic nervous system, in controlling cardiac electrical activity is well described and is primarily mediated by the classical neurotransmitters norepinephrine and acetylcholine.However, emerging evidence suggests that another neurotransmitter system, involving glutamate, the most abundant excitatory neurotransmitter in the nervous system, may participate in governing cardiac excitability and conduction.Glutamate regulates excitability and conductivity of neurons in the central nervous system (CNS).Glutamate exerts its actions via binding to glutamate receptors (GluRs), which comprise ionotropic ligand-gated ion channels (iGluRs) and metabotropic G proteincoupled receptors (mGluRs).It is now recognized that, in addition to their classical localization in the CNS, GluRs are also expressed in peripheral neural and non-neural tissues including heart, kidney, lungs, ovary, testis and endocrine cells. 1 The detection of GluRs in human myocardium, in specific anatomical structures including the nerve fibers, ganglia cells, conducting system, atrial and ventricular cardiomyocytes (CMs), indicates that these receptors and the glutamatergic transmitter system may play a role in the physiology and pathophysiology of vital cardiac functions such as rhythm and excitation. 2 This idea is supported by previous studies reporting an increased incidence and inducibility of ventricular arrhythmias upon activation of the glutamatergic system.For instance, increased systemic levels of glutamate in an ischemia-reperfusion rat model and stimulation of GluRs in rats are associated with ventricular arrhythmias. 3,4lthough the mechanisms underlying arrhythmogenesis in these models remain to be fully explored, cellular and mitochondrial calcium overload, reduced protein expression of potassium channel α (Kv4.2 and Kv4.3, and Kv11.1) and β subunits (KChIP2), as well as changes in the expression and activity of the sarcoplasmic reticulum calcium ATPase (SERCA2A) have been implicated. 3,