PMID- 12611951
OWN - NLM
STAT- MEDLINE
DCOM- 20030702
LR  - 20161124
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 89
IP  - 5
DP  - 2003 May
TI  - Endogenous acetylcholine and nicotine activation enhances GABAergic and 
      glycinergic inputs to cardiac vagal neurons.
PG  - 2473-81
AB  - 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 microM), 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 
      alpha-bungarotoxin but were abolished by dihydro-beta-erythrodine (DHbetaE) at a 
      concentration (3 microM) specific for alpha4beta2 nicotinic receptors. In the 
      presence of TTX, nicotine increased the frequency of GABAergic and glycinergic 
      miniature synaptic events, which were also abolished by DHbetaE (3 microM). This 
      work demonstrates that there is endogenous cholinergic facilitation of GABAergic 
      and glycinergic synaptic inputs to cardiac vagal neurons, and activation of 
      alpha4beta2 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.
FAU - Wang, Jijiang
AU  - Wang J
AD  - Department of Pharmacology, George Washington University, Washington, DC 20037, 
      USA.
FAU - Wang, Xin
AU  - Wang X
FAU - Irnaten, Mustapha
AU  - Irnaten M
FAU - Venkatesan, Priya
AU  - Venkatesan P
FAU - Evans, Cory
AU  - Evans C
FAU - Baxi, Sunit
AU  - Baxi S
FAU - Mendelowitz, David
AU  - Mendelowitz D
LA  - eng
GR  - HL-49965/HL/NHLBI NIH HHS/United States
GR  - HL-59895/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030122
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (GABA Antagonists)
RN  - 0 (Glycine Agents)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Pyridazines)
RN  - 124-87-8 (Picrotoxin)
RN  - 3982TWQ96G (Neostigmine)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - 99460MG420 (gabazine)
RN  - H9Y79VD43J (Strychnine)
RN  - N9YNS0M02X (Acetylcholine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/pharmacology
MH  - Acetylcholine/antagonists & inhibitors/*physiology
MH  - Animals
MH  - Cholinesterase Inhibitors/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Fluorescent Dyes
MH  - GABA Antagonists/pharmacology
MH  - Glycine/*physiology
MH  - Glycine Agents/pharmacology
MH  - Heart/drug effects/*innervation
MH  - Neostigmine/pharmacology
MH  - Neurons/*physiology
MH  - Nicotine/*pharmacology
MH  - Nicotinic Agonists/*pharmacology
MH  - Parasympathetic Nervous System/drug effects/physiology
MH  - Picrotoxin/pharmacology
MH  - Pyridazines/pharmacology
MH  - Rats
MH  - Strychnine/pharmacology
MH  - Synaptic Transmission/drug effects/physiology
MH  - Vagus Nerve/cytology/*physiology
MH  - gamma-Aminobutyric Acid/*physiology
EDAT- 2003/03/04 04:00
MHDA- 2003/07/03 05:00
CRDT- 2003/03/04 04:00
PHST- 2003/03/04 04:00 [pubmed]
PHST- 2003/07/03 05:00 [medline]
PHST- 2003/03/04 04:00 [entrez]
AID - 00934.2002 [pii]
AID - 10.1152/jn.00934.2002 [doi]
PST - ppublish
SO  - J Neurophysiol. 2003 May;89(5):2473-81. doi: 10.1152/jn.00934.2002. Epub 2003 Jan 
      22.