© 1998 American Heart Association, Inc.
Original Contributions |
Nicotine Enhances Presynaptic and Postsynaptic Glutamatergic Neurotransmission to Activate Cardiac Parasympathetic Neurons
From the Department of Physiology and Biophysics, University of Tennessee, Memphis, Tenn.
Correspondence to Dr David Mendelowitz, Department of Physiology and Biophysics, University of Tennessee, 894 Union Ave, Memphis, TN 38163. E-mail dmendel{at}physio1.utmem.edu
Abstract—Although
peripheral cholinergic neurotransmission has long been
known to play a pivotal role in the control of heart rate and blood
pressure, recent evidence has suggested that central cholinergic
mechanisms may be involved in the genesis of hypertension, anxiety,
cardiorespiratory control, and, in particular, the respiratory
modulation of heart rate. Yet, the sites, mechanisms, and receptor
subtypes involved in the action of nicotine within the central nervous
system are controversial. The present study demonstrates that
nicotine has at least 3 sites of action to increase the activity of
vagal cardiac neurons. Nicotine, but not muscarinic agonists,
activates postsynaptic receptors and a depolarizing inward
current in vagal cardiac neurons studied with the perforated
patch-clamp technique in a visualized brain stem slice. In addition,
nicotine acts at different presynaptic and postsynaptic sites to
facilitate glutamatergic neurotransmission. Presynaptic nicotinic
receptors increase the frequency of transmitter release and are
sensitive to block by 
-bungarotoxin. Nicotine also elicits a
previously undescribed augmentation of postsynaptic non-NMDA currents.
The presynaptic and postsynaptic receptors may prove to be future
targets in the search for agonists to increase vagal cardiac activity
and reduce the fatality associated with cardiac hyperexcitability and
for antagonists to reduce cardiac vagal activity in
pathological conditions associated with abnormally low heart rates and
cardiac function such as sudden infant death syndrome.
Key Words: cardiac • parasympathetic • vagal • nicotine • brain stem • sudden infant death syndrome
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