Endogenous Acetylcholine and Nicotine Activation Enhances GABAergic and Glycinergic Inputs to Cardiac Vagal Neurons

2003 ◽  
Vol 89 (5) ◽  
pp. 2473-2481 ◽  
Author(s):  
Jijiang Wang ◽  
Xin Wang ◽  
Mustapha Irnaten ◽  
Priya Venkatesan ◽  
Cory Evans ◽  
...  
Keyword(s):  
Nicotinic Receptors ◽  
Nucleus Ambiguus ◽  
Cholinergic Activity ◽  
Fluorescent Tracer ◽  
Sinus Arrhythmia ◽  
Synaptic Inputs ◽  
Cardiorespiratory Interaction ◽  
Parasympathetic Neurons ◽  
Glycinergic Neurotransmission

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.

Firing properties of identified parasympathetic cardiac neurons in nucleus ambiguus

1996 ◽  
Vol 271 (6) ◽  
pp. H2609-H2614 ◽  
Author(s):  
D. Mendelowitz
Keyword(s):  
Channel Blocker ◽  
Firing Frequency ◽  
Nucleus Ambiguus ◽  
K Channel ◽  
Significant Delay ◽  
Fluorescent Tracer ◽  
Discharge Characteristics ◽  
Firing Properties ◽  
Perforated Patch Clamp

This study tests the hypothesis that identified parasympathetic cardiac neurons in the nucleus ambiguus possess pacemaker-like activity or, alternatively, that these neurons are inherently silent. To test this hypothesis and to examine the firing properties of these neurons, parasympathetic cardiac neurons were identified by the presence of a fluorescent tracer previously applied to their terminals surrounding the heart. Perforated patch-clamp electrophysiological techniques were used to study the spontaneous and depolarization-evoked firing patterns of these identified parasympathetic cardiac neurons in an in vitro brain stem slice. Parasympathetic cardiac neurons were silent. On injection of depolarizing current, however, these neurons fired with both little delay and spike frequency adaptation. Hyperpolarizing prepulses elicited a significant delay before depolarization-evoked firing The Ca(2+)-activated K+ channel blocker apamin, but not charybdotoxin, increased the depolarization-activated firing frequency of these neurons and inhibited the afterhyperpolarization. In summary, parasympathetic cardiac neurons do not have pacemaker-like properties, but they do possess discharge characteristics that would enable them to closely follow excitatory synaptic activation for prolonged periods.

Recruitment of Excitatory Serotonergic Neurotransmission to Cardiac Vagal Neurons in the Nucleus Ambiguus Post Hypoxia and Hypercapnia

2008 ◽  
Vol 99 (3) ◽  
pp. 1163-1168 ◽  
Author(s):  
H. W. Kamendi ◽  
Q. Cheng ◽  
O. Dergacheva ◽  
J. G. Frank ◽  
C. Gorini ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Purinergic Receptor ◽  
Recovery Period ◽  
Nucleus Ambiguus ◽  
P2x Receptor ◽  
Sinus Arrhythmia ◽  
Excitatory Pathways ◽  
Receptor Blockers ◽  
Inspiratory Activity

Inhibitory GABAergic and glycinergic neurotransmission to cardioinhibitory cardiac vagal neurons (CVNs) increase during inspiratory activity and likely mediate respiratory sinus arrhythmia, while the frequency of excitatory postsynaptic currents (EPSCs) in CVNs are unaltered during the different phases of respiration. However, following hypoxia and hypercapnia (H/H), the parasympathetic activity to the heart increases and thus far, identification of the pathways and neurotransmitters that are responsible for exciting CVNs post H/H are unclear. This study identifies different excitatory pathways to CVNs recruited post H/H. Spontaneous and inspiratory-related EPSCs were recorded in CVNs before, during, and after 10 min of H/H in an in vitro slice preparation that retains rhythmic respiratory activity. Before and during H/H, EPSCs in CVNs were completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and d(−)-2-amino-5-phosphonopentanoic acid (AP5), selective AMPA/kainate and N-methyl-d-apartate (NMDA) receptor blockers, respectively. However, after H/H, there was a significant increase in EPSCs during each inspiratory burst. While some of the inspiratory-related EPSCs were blocked by the broad purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-2′, 4′-disulphonic acid (PPADS) and the specific P2X receptor antagonist 2′,3′- O-(2,4,6-trinitrophenyl) adenosine 5′-triphosphate monolithium trisodium salt (TNP-ATP) a P2X receptor blocker, most of the recruited excitatory neurotransmission to CVNs is serotonergic because odansetron, a selective 5-HT3 antagonist, abolished the majority of the spontaneous and inspiratory-related EPSCs evoked during recovery from H/H. The results from this study suggest that following episodes of H/H, two nonglutamatergic excitatory pathways, purinergic and serotonergic, activating P2X and 5-HT3 receptors, respectively, are recruited to excite CVNs in the post H/H recovery period.

Ketamine Inhibits Presynaptic and Postsynaptic Nicotinic Excitation of Identified Cardiac Parasympathetic Neurons in Nucleus Ambiguus

2002 ◽  
Vol 96 (3) ◽  
pp. 667-674 ◽  
Author(s):  
Mustapha Irnaten ◽  
Jijiang Wang ◽  
Priya Venkatesan ◽  
Cory Evans ◽  
Kyoung S. K. Chang ◽  
...  
Keyword(s):  
Heart Rate ◽  
Glutamate Release ◽  
Cardiac Activity ◽  
Presynaptic Receptors ◽  
Nucleus Ambiguus ◽  
Patch Clamp Recording ◽  
Preganglionic Neurons ◽  
Parasympathetic Neurons ◽  
Alpha Bungarotoxin

Background Ketamine increases both blood pressure and heart rate, effects commonly thought of as sympathoexcitatory. The authors investigated possible central nervous system actions of ketamine to inhibit cardiac parasympathetic neurons in the brainstem by inhibiting multiple nicotinic excitatory mechanisms. Methods The authors used a novel in vitro approach to study the effect of ketamine on identified cardiac parasympathetic preganglionic neurons in rat brainstem slices. The cardiac parasympathetic neurons in the nucleus ambiguus were retrogradely prelabeled with the fluorescent tracer by placing rhodamine into the pericardial sac. Dye-labeled neurons were visually identified for patch clamp recording. The effects of ketamine were tested on nicotine-evoked ligand-gated currents and spontaneous glutamatergic miniature synaptic currents (mini) in cardiac parasympathetic preganglionic neurons. Results Ketamine (10 microm) inhibited (1) the nicotine (1 microm)-evoked presynaptic facilitation of glutamate release (mini frequency, 18 +/- 7% of control; n = 9), and (2) the direct postsynaptic ligand-gated current (27 +/- 8% of control; n = 9), but ketamine did not alter the amplitude of postsynaptic miniature non-N-methyl-D-aspartate currents. alpha Bungarotoxin, an antagonist of alpha 7 containing nicotinic presynaptic receptors, blocked ketamine actions on mini frequency (n = 10) but not mini amplitude. Conclusions Ketamine inhibits the presynaptic nicotinic receptors responsible for facilitating neurotransmitter release, as well as the direct ligand-gated inward current, but does not alter the nicotinic augmentation of non-N-methyl-D-aspartate currents in brainstem parasympathetic cardiac neurons. Such actions may mediate the decrease in parasympathetic cardiac activity and increase in heart rate that occurs with ketamine.

Propofol Modulates γ-Aminobutyric Acid–mediated Inhibitory Neurotransmission to Cardiac Vagal Neurons in the Nucleus Ambiguus

2004 ◽  
Vol 100 (5) ◽  
pp. 1198-1205 ◽  
Author(s):  
Xin Wang ◽  
Zheng-Gui Huang ◽  
Allison Gold ◽  
Evguenia Bouairi ◽  
Cory Evans ◽  
...  
Keyword(s):  
Heart Rate ◽  
Decay Time ◽  
Nucleus Ambiguus ◽  
Aminobutyric Acid ◽  
Gabaergic Neurotransmission ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Inhibitory Neurotransmission ◽  
Parasympathetic Neurons ◽  
Glycinergic Neurotransmission

Background Although it is well recognized that anesthetics modulate the central control of cardiorespiratory homeostasis, the cellular mechanisms by which anesthetics alter cardiac parasympathetic activity are poorly understood. One common site of action of anesthetics is inhibitory neurotransmission. This study investigates the effect of propofol on gamma-aminobutyric acid-mediated (GABAergic) and glycinergic neurotransmission to cardiac parasympathetic neurons. Methods Cardiac parasympathetic neurons were identified in vitro by the presence of a retrograde fluorescent tracer, and spontaneous GABAergic and glycinergic synaptic currents were examined using whole cell patch clamp techniques. Results Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) increased the duration and decay time of spontaneous GABAergic inhibitory postsynaptic currents. To determine whether the action of propofol was at presynaptic or postsynaptic sites, tetrodotoxin was applied to isolate miniature inhibitory postsynaptic currents. Propofol at concentrations of 1.0 microm and greater significantly (P < 0.05) prolonged the decay time and duration of miniature inhibitory postsynaptic currents, indicating that propofol directly alters GABAergic neurotransmission at a postsynaptic site. Propofol at high concentrations (> or =50 microm) also inhibited the frequency of both GABAergic inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents. Propofol at concentrations up to 50 microm had no effect on glycinergic neurotransmission. Conclusions Propofol may vary heart rate by modulating GABAergic neurotransmission to cardiac parasympathetic neurons. At clinically relevant concentrations (> or =1.0 microm), propofol facilitated GABAergic responses in cardiac vagal neurons by increasing decay time, which would increase inhibition of cardioinhibitory cardiac vagal neurons and evoke an increase in heart rate. At higher supraclinical concentrations (> or =50 microm), propofol inhibits GABAergic neurotransmission to cardiac vagal neurons, which would evoke a decrease in heart rate.

Ketamine Inhibits Inspiratory-evoked γ-Aminobutyric Acid and Glycine Neurotransmission to Cardiac Vagal Neurons in the Nucleus Ambiguus

2005 ◽  
Vol 103 (2) ◽  
pp. 353-359 ◽  
Author(s):  
Xin Wang ◽  
Zheng-Gui Huang ◽  
Olga Dergacheva ◽  
Evguenia Bouairi ◽  
Christopher Gorini ◽  
...  
Keyword(s):  
Respiratory Activity ◽  
Nucleus Ambiguus ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Burst Frequency ◽  
Sinus Arrhythmia ◽  
Emergency Situations ◽  
Perioperative Pain Management ◽  
Efferent Neurons ◽  
Glycinergic Neurotransmission

Background Ketamine can be used for perioperative pain management as well as a dissociative anesthetic agent in emergency situations. However, ketamine can induce both cardiovascular and respiratory depression, especially in pediatric patients. Although ketamine has usually been regarded as sympathoexcitatory, recent work has demonstrated that ketamine has important actions on parasympathetic cardiac vagal efferent activity. The current study tests the hypothesis that ketamine, at clinical relevant concentrations, alters central cardiorespiratory interactions in the brainstem and, in particular, the inspiration-evoked increase in gamma-aminobutyric acid-mediated and glycinergic neurotransmission to parasympathetic cardiac efferent neurons. Methods Cardiac vagal neurons were identified by the presence of a retrograde fluorescent tracer. Respiratory evoked gamma-aminobutyric acid-mediated and glycinergic synaptic currents were recorded in cardiac vagal neurons using whole cell patch clamp techniques while spontaneous rhythmic respiratory activity was recorded simultaneously. Results : Ketamine, at concentrations from 0.1 to 10 microM, evoked a concentration-dependent inhibition of inspiratory burst frequency. Inspiration-evoked gamma-aminobutyric acid-mediated neurotransmission to cardiac vagal neurons was inhibited at ketamine concentrations of 0.5 and 1 microM. The increase in glycinergic activity to cardiac vagal neurons during inspiration was also inhibited at ketamine concentrations of 0.5 and 1 microM. Conclusions At clinically relevant concentrations (0.5 and 1 microM), ketamine alters central respiratory activity and diminishes both inspiration-evoked gamma-aminobutyric acid-mediated and glycinergic neurotransmission to parasympathetic cardiac efferent neurons. This reduction in inhibitory neurotransmission to cardiac vagal neurons is likely responsible for the compromised respiratory sinus arrhythmia that occurs with ketamine anesthesia.

scholarly journals High-Affinity Nicotinic Receptors Modulate Spontaneous Cortical Up States In Vitro

2015 ◽  
Vol 35 (32) ◽  
pp. 11196-11208 ◽  
Author(s):  
C. Sigalas ◽  
P. Rigas ◽  
P. Tsakanikas ◽  
I. Skaliora
Keyword(s):  
Nicotinic Receptors ◽  
High Affinity ◽  
Up States

scholarly journals Inositol incorporation into phosphoinositides in retinal horizontal cells of Xenopus laevis: enhancement by acetylcholine, inhibition by glycine.

1984 ◽  
Vol 99 (2) ◽  
pp. 686-691 ◽  
Author(s):  
R E Anderson ◽  
J G Hollyfield
Keyword(s):  
Xenopus Laevis ◽  
Culture Medium ◽  
Photoreceptor Cells ◽  
Horizontal Cells ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Light Effect ◽  
Synaptic Inputs ◽  
Absorption Of Light

The absorption of light by photoreceptor cells leads to an increased incorporation of [2-3H]inositol into phosphoinositides of horizontal cells in the retina of Xenopus laevis in vitro. We have identified several retinal neurotransmitters that are involved in regulating this response. Incubation with glycine, the neurotransmitter of an interplexiform cell that has direct synaptic input onto horizontal cells, abolishes the light effect. This inhibition is reversed by preincubation with strychnine. Acetylcholine added to the culture medium enhances the incorporation of [2-3H]inositol into phosphoinositides in horizontal cells when retinas are incubated in the dark. This effect is inhibited by preincubation with atropine. However, atropine alone does not inhibit the light-enhanced incorporation of [2-3H]inositol into phosphoinositides in the retina. gamma-Aminobutyric acid, the neurotransmitter of retinal horizontal cells in X. laevis, as well as dopamine and norepinephrine, have no effect on the incorporation of [2-3H]inositol into phosphoinositides. These studies demonstrate that the light-enhanced incorporation of [2-3H]inositol into phosphoinositides of retinal horizontal cells is regulated by specific neurotransmitters, and that there are probably several synaptic inputs into horizontal cells which control this process.

Properties of synaptic inputs from myenteric neurons innervating submucosal S neurons in guinea pig ileum

2000 ◽  
Vol 278 (2) ◽  
pp. G273-G280 ◽  
Author(s):  
B. A. Moore ◽  
S. Vanner
Keyword(s):  
Guinea Pig ◽  
Myenteric Plexus ◽  
Intracellular Recordings ◽  
Guinea Pig Ileum ◽  
Myenteric Neurons ◽  
Synaptic Inputs ◽  
Stimulus Train ◽  
Stimulation Of ◽  
Double Chamber

This study examined synaptic inputs from myenteric neurons innervating submucosal neurons. Intracellular recordings were obtained from submucosal S neurons in guinea pig ileal preparations in vitro, and synaptic inputs were recorded in response to electrical stimulation of exposed myenteric plexus. Most S neurons received synaptic inputs [>80% fast (f) excitatory postsynaptic potentials (EPSP), >30% slow (s) EPSPs] from the myenteric plexus. Synaptic potentials were recorded significant distances aboral (fEPSPs, 25 mm; sEPSPs, 10 mm) but not oral to the stimulating site. When preparations were studied in a double-chamber bath that chemically isolated the stimulating “myenteric chamber” from the recording side “submucosal chamber,” all fEPSPs were blocked by hexamethonium in the submucosal chamber, but not by a combination of nicotinic, purinergic, and 5-hydroxytryptamine-3 receptor antagonists in the myenteric chamber. In 15% of cells, a stimulus train elicited prolonged bursts of fEPSPs (>30 s duration) that were blocked by hexamethonium. These findings suggest that most submucosal S neurons receive synaptic inputs from predominantly anally projecting myenteric neurons. These inputs are poised to coordinate intestinal motility and secretion.

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