Nicotine enhances presynaptic and postsynaptic glutamatergic neurotransmission to activate cardiac parasympathetic neurons.
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 alpha-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.
Neff
R A
RA
Department of Physiology and Biophysics, University of Tennessee, Memphis, TN, USA.
Humphrey
J
J
Mihalevich
M
M
Mendelowitz
D
D
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003472:Curare / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000294:innervation; D066298:In Vitro Techniques; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D011950:Receptors, Cholinergic / Q000096:biosynthesis / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018733:Nicotinic Antagonists; D011950:Receptors, Cholinergic; D018698:Glutamic Acid; D009538:Nicotine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D003472:Curare; D000109:Acetylcholine