Volume 940, Issue 1 p. 237-246

Synaptic and Neurotransmitter Activation of Cardiac Vagal Neurons in the Nucleus Ambiguus

JIJIANG WANG

JIJIANG WANG

Department of Pharmacology, George Washington University, Washington, District of Columbia 20037, USA

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MUSTAPHA IRNATEN

MUSTAPHA IRNATEN

Department of Pharmacology, George Washington University, Washington, District of Columbia 20037, USA

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ROBERT A. NEFF

ROBERT A. NEFF

Department of Pharmacology, George Washington University, Washington, District of Columbia 20037, USA

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PRIYA VENKATESAN

PRIYA VENKATESAN

Department of Pharmacology, George Washington University, Washington, District of Columbia 20037, USA

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CORY EVANS

CORY EVANS

Department of Pharmacology, George Washington University, Washington, District of Columbia 20037, USA

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ARTHUR D. LOEWY

ARTHUR D. LOEWY

Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA

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THOMAS C. METTENLEITER

THOMAS C. METTENLEITER

Federal Research Center for Virus Diseases of Animals, Institute of Molecular Biology, Friedrich-Loeffler Institutes, D-17498 Insel Riems, Germany

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DAVID MENDELOWITZ

Corresponding Author

DAVID MENDELOWITZ

Department of Pharmacology, George Washington University, Washington, District of Columbia 20037, USA

d Address for correspondence: David Mendelowitz, Department of Pharmacology, George Washington University, 2300 Eye St. NW, Washington, D.C. 20037. Voice: 202-994-3466; fax: 202-994-2870. [email protected]Search for more papers by this author
First published: 25 January 2006
Citations: 111

Abstract

Abstract: 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.