Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons

Document Type

Journal Article

Publication Date



Journal of Neurophysiology








The heart slows during expiration and heart rate increases during inspiration. This cardiorespiratory interaction is thought to occur by increased inhibitory synaptic events to cardiac vagal neurons during inspiration. Since cholinergic receptors have been suggested to be involved in this cardiorespiratory interaction, we tested whether endogenous cholinergic activity modulates GABAergic and glycinergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus, whether nicotine can mimic this facilitation, and we examined the nicotinic receptors involved. Cardiac vagal neurons in the rat were labeled with a retrograde fluorescent tracer and studied in an in vitro slice using patch-clamp techniques. Application of neostigmine (10 μM), an acetylcholinerase inhibitor, significantly increased the frequency of both GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) in cardiac vagal neurons. Exogenous application of nicotine increased the frequency and amplitude of both GABAergic and glycinergic IPSCs. The nicotinic facilitation of both GABAergic and glycinergic IPSCs were insensitive to 100 nM α-bungarotoxin but were abolished by dihydro-β-erythrodine (DHβE) at a concentration (3 μM) specific for α4β2 nicotinic receptors. In the presence of TTX, nicotine increased the frequency of GABAergic and glycinergic miniature synaptic events, which were also abolished by DHβE (3 μM). This work demonstrates that there is endogenous cholinergic facilitation of GABAergic and glycinergic synaptic inputs to cardiac vagal neurons, and activation of α4β2 nicotinic receptors at presynaptic terminals facilitates GABAergic and glycinergic neurotransmission to cardiac vagal neurons. Nicotinic facilitation of inhibitory neurotransmission to premotor cardiac parasympathetic neurons may be involved in generating respiratory sinus arrhythmia.

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