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J Neurophysiol (May 1, 2003). 10.1152/jn.00934.2002
Submitted on Submitted 25 October 2002; accepted in final form 14 January 2003
Department of Pharmacology, George Washington University, Washington, DC 20037
Wang, Jijiang,
Xin Wang,
Mustapha Irnaten,
Priya Venkatesan,
Cory Evans,
Sunit Baxi, and
David Mendelowitz.
Endogenous Acetylcholine and Nicotine Activation Enhances
GABAergic and Glycinergic Inputs to Cardiac Vagal Neurons. J. Neurophysiol. 89: 2473-2481, 2003. 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
-bungarotoxin but were
abolished by dihydro-
-erythrodine (DH
E) at a concentration (3 µM) specific for
4
2 nicotinic receptors. In the presence of
TTX, nicotine increased the frequency of GABAergic and glycinergic
miniature synaptic events, which were also abolished by DH
E (3 µM). This work demonstrates that there is endogenous cholinergic
facilitation of GABAergic and glycinergic synaptic inputs to cardiac
vagal neurons, and activation of
4
2 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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