Nicotine enhances presynaptic and postsynaptic glutamatergic neurotransmission to activate cardiac parasympathetic neurons

Although peripheral cholinergic neurotransmission has long been known to pl ay a pivotal role in the control of heart rate and blood pressure, recent e vidence has suggested that central cholinergic mechanisms may be involved i n the genesis of hypertension, anxiety, cardiorespiratory control, and, in particular, the respiratory modulation of heart rate. Yet, the sites, mecha nisms, and receptor subtypes involved in the action of nicotine within the central nervous system are controversial. The present study demonstrates th at nicotine has at least 3 sites of action to increase the activity of vaga l cardiac neurons. Nicotine, but not muscarinic agonists, activates postsyn aptic receptors and a depolarizing inward current in vagal cardiac neurons studied with the perforated patch-clamp technique in a visualized brain ste m slice. Ln addition, nicotine acts at different presynaptic and postsynapt ic sites to facilitate glutamatergic neurotransmission. Presynaptic nicotin ic receptors increase the frequency of transmitter release and are sensitiv e to block by cu-bungarotoxin. Nicotine also elicits a previously undescrib ed augmentation of postsynaptic non-NMDA currents. The presynaptic and post synaptic receptors may prove to be future targets in the search for agonist s to increase vagal cardiac activity and reduce the fatality associated wit h cardiac hyperexcitability and for antagonists to reduce cardiac vagal act ivity in pathological conditions associated with abnormally low heart rates and cardiac function such as sudden infant death syndrome.