Synaptic and neurotransmitter activation of cardiac vagal neurons in the nucleus ambiguus.
Cardiac vagal neurons play a critical role in the control of heart rate and cardiac function. These neurons, which are primarily located in the nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DMNX), dominate the neural control of heart rate under normal conditions. Cardiac vagal activity is diminished and unresponsive in many disease states, while restoration of parasympathetic activity to the heart lessens ischemia and arrhythmias and decreases the risk of sudden death. Recent work has demonstrated that cardiac vagal neurons are intrinsically silent and therefore rely on synaptic input to control their firing. To date, three major synaptic inputs to cardiac vagal neurons have been identified. Stimulation of the nucleus tractus solitarius evokes a glutamatergic pathway that activates both NMDA and non-NMDA glutamatergic postsynaptic currents in cardiac vagal neurons. Acetylcholine excites cardiac vagal neurons via three mechanisms, activating a direct ligand-gated postsynaptic nicotinic receptor, enhancing postsynaptic non-NMDA currents, and presynaptically by facilitating transmitter release. This enhancement by nicotine is dependent upon activation of pre- and postsynaptic P-type voltage-gated calcium channels. Additionally, there is a GABAergic innervation of cardiac vagal neurons. The transsynaptic pseudorabies virus that expresses GFP (PRV-GFP) has been used to identify, for subsequent electrophysiologic study, neurons that project to cardiac vagal neurons. Bartha PRV-GFP-labeled neurons retain their normal electrophysiological properties, and the labeled baroreflex pathways that control heart rate are unaltered by the virus.
Wang
J
J
Department of Pharmacology, George Washington University, 2300 Eye St. NW, Washington, D.C. 20037, USA.
Irnaten
M
M
Neff
R A
RA
Venkatesan
P
P
Evans
C
C
Loewy
A D
AD
Mettenleiter
T C
TC
Mendelowitz
D
D
D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006321:Heart / Q000294:innervation*; D006801:Humans; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018377:Neurotransmitter Agents; D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid