scholarly journals Effect of Extracellular Calcium on Excitability of Guinea Pig Airway Vagal Afferent Nerves

2003 ◽  
Vol 89 (3) ◽  
pp. 1196-1204 ◽  
Author(s):  
Bradley J. Undem ◽  
Eun Joo Oh ◽  
Eric Lancaster ◽  
Daniel Weinreich
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Extracellular Calcium ◽  
C Fibers ◽  
Afferent Nerves ◽  
Nodose Ganglia ◽  
Cation Conductance ◽  
Afferent Fibers ◽  
Low Threshold ◽  
Vagal Afferent

The effect of reducing extracellular calcium concentration ([Ca2+]o) on vagal afferent excitability was analyzed in a guinea pig isolated vagally innervated trachea-bronchus preparation. Afferent fibers were characterized as either having low-threshold, rapidly adapting mechanosensors (Aδ fibers) or nociceptive-like phenotypes (Aδ and C fibers). The nociceptors were derived from neurons within the jugular ganglia, whereas the low-threshold mechanosensors were derived from neurons within the nodose ganglia. Reducing [Ca2+]o did not affect the excitability of the low-threshold mechanosensors in the airway. By contrast, reducing [Ca2+]o selectively increased the excitability of airway nociceptors as manifested by a substantive increase in action potential discharge in response to mechanical stimulation, and in a subset of fibers, by overtly evoking action potential discharge. This increase in the excitability of nociceptors was not mimicked by a combination of ω-conotoxin and nifedipine or tetraethylammonium. Whole cell patch recordings from airway-labeled and unlabeled neurons in the vagal jugular ganglia support the hypothesis that [Ca2+]o inhibits a nonselective cation conductance in vagal nociceptors that may serve to regulate excitability of the nerve terminals within the airways.

scholarly journals Selective inhibition of vagal afferent nerve pathways regulating cough using Nav 1.7 shRNA silencing in guinea pig nodose ganglia

2013 ◽  
Vol 304 (11) ◽  
pp. R1017-R1023 ◽  
Author(s):  
Yukiko Muroi ◽  
Fei Ru ◽  
Yang-Ling Chou ◽  
Michael J. Carr ◽  
Bradley J. Undem ◽  
...  
Keyword(s):  
Action Potential ◽  
Guinea Pigs ◽  
Fluorescent Protein ◽  
Nerve Fibers ◽  
Vagal Nerve ◽  
Afferent Nerve ◽  
Tracheal Mucosa ◽  
C Fibers ◽  
Nodose Ganglia ◽  
Vagal Afferent

Adeno-associated virus delivery systems and short hairpin RNA (shRNA) were used to selectively silence the voltage-gated sodium channel NaV 1.7 in the nodose ganglia of guinea pigs. The cough reflex in these animals was subsequently assessed. NaV 1.7 shRNA was delivered to the majority of nodose ganglia neurons [50–60% transfection rate determined by green fluorescent protein (GFP) gene cotransfection] and action potential conduction in the nodose vagal nerve fibers, as evaluated using an extracellular recording technique, was markedly and significantly reduced. By contrast, <5% of neurons in the jugular vagal ganglia neurons were transfected, and action potential conduction in the jugular vagal nerve fibers was unchanged. The control virus (with GFP expression) was without effect on action potential discharge and conduction in either ganglia. In vivo, NaV 1.7 silencing in the nodose ganglia nearly abolished cough evoked by mechanically probing the tracheal mucosa in anesthetized guinea pigs. Stimuli such as capsaicin and bradykinin that are known to stimulate both nodose and jugular C-fibers evoked coughing in conscious animals was unaffected by NaV 1.7 silencing in the nodose ganglia. Nodose C-fiber selective stimuli including adenosine, 2-methyl-5-HT, and ATP all failed to evoke coughing upon aerosol challenge. These results indicate that cough is independently regulated by two vagal afferent nerve subtypes in guinea pigs, with nodose Aδ fibers regulating cough evoked mechanically from the trachea and bradykinin- and capsaicin-evoked cough regulated by C-fibers arising from the jugular ganglia.

Endogenous CCK disrupts the MMC pattern via capsaicin-sensitive vagal afferent fibers in the rat

1997 ◽  
Vol 272 (1) ◽  
pp. G100-G105 ◽  
Author(s):  
A. Rodriguez-Membrilla ◽  
P. Vergara
Keyword(s):  
Intravenous Infusion ◽  
Sprague Dawley ◽  
Rat Intestine ◽  
Intracerebroventricular Infusion ◽  
C Fibers ◽  
Afferent Fibers ◽  
Sprague Dawley Rats ◽  
Vagal Afferent ◽  
Endogenous Release ◽  
Stimulation Of

A meal disrupts migrating motor complexes (MMC) in the rat intestine through stimulation of peripheral cholecystokinin (CCK)-B and central CCK-A receptors. The aim of this study was to determine pathways implicated in postprandial disruption of the MMC mediated by CCK. Sprague-Dawley rats were prepared with electrodes for electromyography in the small intestine, and ablation of vagal afferent C-fibers by capsaicin was carried out. Endogenous release of CCK was induced by oral administration of soybean trypsin inhibitor (SBTI). In control rats SBTI disrupted MMC and generated an irregular spiking activity that lasted longer than 3 h. Intravenous infusion of L-365,260 (2 x 10(-7) mol/kg) but not of L-364,718 (3 x 10(-9) mol/kg) restored the MMC pattern. In capsaicin-treated rats, SBTI did not modify fasting activity. Infusion of CCK octapeptide (CCK-8) at 3 x 10(-9) mol.kg-1.h-1 disrupted the MMC, although the response was quantitatively and qualitatively different from SBTI. The effect was reversed by intravenous infusion of L-364,718 or L-365,260 and intracerebroventricular infusion of L-364,718. In capsaicin-treated rats, the intracerebroventricular or intravenous infusion of L-364,718 inhibited CCK-8 effects. However, the intravenous infusion of L-365,260 did not reverse the MMC pattern. These results suggest that the disruption of the MMC mediated by CCK is due to stimulation of peripheral CCK-B receptors located in vagal afferent fibers. This initiates a reflex including stimulation of central CCK-A receptors. Exogenous CCK also stimulates peripheral CCK-A receptors not located in capsaicin-sensitive vagal afferent fibers.

scholarly journals Kv1.3 channels regulate synaptic transmission in the nucleus of solitary tract

2011 ◽  
Vol 105 (6) ◽  
pp. 2772-2780 ◽  
Author(s):  
Angelina Ramirez-Navarro ◽  
Patricia A. Glazebrook ◽  
Michelle Kane-Sutton ◽  
Caroline Padro ◽  
David D. Kline ◽  
...  
Keyword(s):  
Action Potential ◽  
Transmitter Release ◽  
Brain Slices ◽  
Presynaptic Terminal ◽  
Solitary Tract ◽  
Sensory Afferents ◽  
Peripheral Neurons ◽  
C Fibers ◽  
Nodose Ganglia ◽  
Nucleus Of Solitary Tract

The voltage-gated K+ channel Kv1.3 has been reported to regulate transmitter release in select central and peripheral neurons. In this study, we evaluated its role at the synapse between visceral sensory afferents and secondary neurons in the nucleus of the solitary tract (NTS). We identified mRNA and protein for Kv1.3 in rat nodose ganglia using RT-PCR and Western blot analysis. In immunohistochemical experiments, anti-Kv1.3 immunoreactivity was very strong in internal organelles in the soma of nodose neurons with a weaker distribution near the plasma membrane. Anti-Kv1.3 was also identified in the axonal branches that project centrally, including their presynaptic terminals in the medial and commissural NTS. In current-clamp experiments, margatoxin (MgTx), a high-affinity blocker of Kv1.3, produced an increase in action potential duration in C-type but not A- or Ah-type neurons. To evaluate the role of Kv1.3 at the presynaptic terminal, we examined the effect of MgTx on tract evoked monosynaptic excitatory postsynaptic currents (EPSCs) in brain slices of the NTS. MgTx increased the amplitude of evoked EPSCs in a subset of neurons, with the major increase occurring during the first stimuli in a 20-Hz train. These data, together with the results from somal recordings, support the hypothesis that Kv1.3 regulates the duration of the action potential in the presynaptic terminal of C fibers, limiting transmitter release to the postsynaptic cell.

Role of NaV1.7 in Action Potential Conduction along Human Bronchial Vagal Afferent C‐fibers

2021 ◽  
Author(s):  
Marian Kollarik ◽  
Fei Ru ◽  
Nikoleta Pavelkova ◽  
John Mulcahy ◽  
John Hunter ◽  
...  
Keyword(s):  
Action Potential ◽  
C Fibers ◽  
Vagal Afferent

scholarly journals Subdiaphragmatic vagal afferent nerves modulate visceral pain

2008 ◽  
Vol 294 (6) ◽  
pp. G1441-G1449 ◽  
Author(s):  
S. L. Chen ◽  
X. Y. Wu ◽  
Z. J. Cao ◽  
J. Fan ◽  
M. Wang ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
High Intensity ◽  
Visceral Pain ◽  
Light Level ◽  
Vagal Afferents ◽  
Abdominal Muscles ◽  
Low Intensity ◽  
C Fibers ◽  
Afferent Nerves ◽  
Vagal Afferent

Activation of the vagal afferents by noxious gastrointestinal stimuli suggests that vagal afferents may play a complex role in visceral pain processes. The contribution of the vagus nerve to visceral pain remains unresolved. Previous studies reported that patients following chronic vagotomy have lower pain thresholds. The patient with irritable bowel syndrome has been shown alteration of vagal function. We hypothesize that vagal afferent nerves modulate visceral pain. Visceromotor responses (VMR) to graded colorectal distension (CRD) were recorded from the abdominal muscles in conscious rats. Chronic subdiaphragmatic vagus nerve sections induced 470, 106, 51, and 54% increases in VMR to CRD at 20, 40, 60 and 80 mmHg, respectively. Similarly, at light level of anesthesia, topical application of lidocaine to the subdiaphragmatic vagus nerve in rats increased VMR to CRD. Vagal afferent neuronal responses to low or high-intensity electrical vagal stimulation (EVS) of vagal afferent Aδ or C fibers were distinguished by calculating their conduction velocity. Low-intensity EVS of Aδ fibers (40 μA, 20 Hz, 0.5 ms for 30 s) reduced VMR to CRD at 40, 60, and 80 mmHg by 41, 52, and 58%, respectively. In contrast, high-intensity EVS of C fibers (400 μA, 1 Hz, 0.5 ms for 30 s) had no effect on VMR to CRD. In conclusion, we demonstrated that vagal afferent nerves modulate visceral pain. Low-intensity EVS that activates vagal afferent Aδ fibers reduced visceral pain. Thus EVS may potentially have a role in the treatment of chronic visceral pain.

Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs

2006 ◽  
Vol 291 (2) ◽  
pp. R454-R463 ◽  
Author(s):  
Brendan J. Canning ◽  
David G. Farmer ◽  
Nanako Mori
Keyword(s):  
Citric Acid ◽  
Guinea Pigs ◽  
Transient Receptor Potential ◽  
Superior Laryngeal Nerve ◽  
Transient Receptor Potential Vanilloid ◽  
Receptor Antagonists ◽  
Tracheal Mucosa ◽  
C Fibers ◽  
Afferent Nerves ◽  
Vagal Afferent

Experiments carried out in conscious guinea pigs suggest that citric acid-evoked coughing is partly mediated by transient receptor potential vanilloid type 1 (TRPV1) receptor-dependent activation of tachykinin-containing, capsaicin-sensitive C fibers. In vitro electrophysiological analyses indicate, however, that acid also activates capsaicin-sensitive and -insensitive vagal afferent nerves by a TRPV1-independent mechanism, and studies in anesthetized guinea pigs show that coughing evoked by acid is mediated by activation of capsaicin-insensitive vagal afferent nerves. In the present study, we have characterized the mechanisms of citric acid-evoked coughing in anesthetized guinea pigs. Drugs were administered directly to the Krebs buffer perfusing the extrathoracic trachea. Citric acid was applied topically to the tracheal mucosa, directly into the tracheal perfusate in increasing concentrations and at 1-min intervals. Citric acid dose dependently evoked coughing in anesthetized guinea pigs. This was mimicked by hydrochloric acid but not by sodium citrate. The coughing evoked by acid was nearly or completely abolished by TTX or by cutting the recurrent laryngeal nerves. Perfusing the trachea with a low Cl− buffer potentiated the acid-induced cough reflex. In contrast, prior capsaicin desensitization, 10 μM capsazepine, Ca2+-free perfusate, 0.1 μM iberiotoxin, 1 μM atropine, 10 μM isoproterenol, 10 μM albuterol, 3 μM indomethacin, 0.1 μM HOE-140, a combination of neurokinin1 (NK1; CP-99994), NK2 (SR-48968), and NK3 (SB-223412) receptor antagonists (0.1 μM each), a combination of histamine H1 (3 μM pyrilamine) and cysLT1 (1 μM ICI-198615) receptor antagonists, superior laryngeal nerve transection, or epithelium removal did not inhibit citric acid-evoked coughing. These and other data indicate that citric acid-evoked coughing in anesthetized guinea pigs is mediated by direct activation of capsaicin-insensitive vagal afferent nerves, perhaps through sequential activation of acid-sensing ion channels and chloride channels.

Cholecystokinin increases cytosolic calcium in a subpopulation of cultured vagal afferent neurons

2002 ◽  
Vol 283 (6) ◽  
pp. R1303-R1313 ◽  
Author(s):  
Steven M. Simasko ◽  
Jason Wiens ◽  
Adrienne Karpiel ◽  
Mihai Covasa ◽  
Robert C. Ritter
Keyword(s):  
Cytosolic Calcium ◽  
Threshold Concentration ◽  
Extracellular Calcium ◽  
Calcium Stores ◽  
Afferent Neurons ◽  
Sensory Stimuli ◽  
Adult Rat ◽  
Nodose Ganglia ◽  
Vagal Afferent ◽  
High Concentrations

Imaging fluorescent measurements with fura 2 were used to examine cytosolic calcium signals induced by sulfated CCK octapeptide (CCK-8) in dissociated vagal afferent neurons from adult rat nodose ganglia. We found that 40% (184/465) of the neurons responded to CCK-8 with a transient increase in cytosolic calcium. The threshold concentration of CCK-8 for inducing the response varied from 0.01 to 100 nM. In most neurons (13/16) the response was eliminated by removing extracellular calcium. Depleting intracellular calcium stores with thapsigargin slightly augmented the response. Most neurons were unresponsive to nonsulfated CCK-8. The response was eliminated by the CCK-A receptor antagonist lorglumide. Low concentrations of JMV-180 had no effect; however, high concentrations of JMV-180 reduced responses to CCK-8. These results demonstrate that CCK acts at the low-affinity site of the CCK-A receptor to trigger the entry of extracellular calcium into vagal afferent neurons. Increased cytosolic calcium may participate in acute activation of vagal afferent neurons, or it may initiate long-term changes, which modulate future neuronal responses to sensory stimuli.

scholarly journals Differential effects of airway afferent nerve subtypes on cough and respiration in anesthetized guinea pigs

2008 ◽  
Vol 295 (5) ◽  
pp. R1572-R1584 ◽  
Author(s):  
Yang-Ling Chou ◽  
Mark D. Scarupa ◽  
Nanako Mori ◽  
Brendan J. Canning
Keyword(s):  
Citric Acid ◽  
Hypertonic Saline ◽  
Guinea Pigs ◽  
Afferent Nerve ◽  
Vagal Afferents ◽  
C Fibers ◽  
Afferent Nerves ◽  
Nodose Ganglia ◽  
Opposing Effects ◽  
Respiratory Reflexes

The hypothesis that respiratory reflexes, such as cough, reflect the net and often opposing effects of activation of multiple afferent nerve subpopulations throughout the airways was evaluated. Laryngeal and tracheal mucosal challenge with either citric acid or mechanical probing reliably evoked coughing in anesthetized guinea pigs. No other stimulus reliably evoked coughing in these animals, regardless of route of administration and despite some profound effects on respiration. Selectively activating vagal C-fibers arising from the nodose ganglia with either adenosine or 2-methyl-5-HT evoked only tachypnea. Selectively activating vagal afferents arising from the jugular ganglia induced respiratory slowing and apnea. Nasal afferent nerve activation by capsaicin, citric acid, hypertonic saline, or histamine evoked only respiratory slowing. Histamine, which activates intrapulmonary rapidly adapting receptors but not airway or lung C-fibers or tracheal bronchial cough receptors induced bronchospasm and tachypnea, but no coughing. The results indicate that the reflexes initiated by stimuli thought to be selective for some afferent nerve subtypes will likely depend on the net and potentially opposing effects of multiple afferent nerve subpopulations throughout the airways. The data also provide further evidence that the afferent nerves regulating cough in anesthetized guinea pigs are distinct from either C-fibers or intrapulmonary rapidly adapting receptors.

Inhibitory effects on intake of cholecystokinin-8 and cholecystokinin-33 in rats with hepatic proper or common hepatic branch vagal innervation

2005 ◽  
Vol 289 (2) ◽  
pp. R456-R462 ◽  
Author(s):  
S. Eisen ◽  
R. J. Phillips ◽  
N. Geary ◽  
E. A. Baronowsky ◽  
T. L. Powley ◽  
...  
Keyword(s):  
Intraperitoneal Administration ◽  
Inhibitory Effect ◽  
Inhibitory Interaction ◽  
Afferent Nerves ◽  
Afferent Fibers ◽  
Vagal Nerves ◽  
Vagal Innervation ◽  
Afferent Vagal ◽  
Vagal Afferent ◽  
Hepatic Branch

The relative potencies of cholecystokinin (CCK)-8 and CCK-33 for decreasing meal size depend on the route of administration. Inhibitory potencies are equal after intraperitoneal administration, but CCK-33 is significantly more potent after intraportal administration. This suggests that CCK-33 is a more effective stimulant of hepatic afferent vagal nerves than is CCK-8. To investigate this possibility, we administered both peptides intraperitoneally in rats with abdominal vagotomies that spared only the hepatic proper vagal nerves (H) and in rats with abdominal vagotomies that spared the common hepatic branch that contains the fibers of the hepatic proper and gastroduodenal nerves (HGD). The vagal afferent innervation in H and HGD rats was verified with a wheat germ agglutinin-horseradish tracer strategy. Intraperitoneal administration of CCK-33 decreased 30-min intake of 10% sucrose in H rats as much as in sham rats, but CCK-8 decreased intake significantly less in H rats than in sham rats. The larger inhibitory effect of CCK-33 than of CCK-8 in H rats is consistent with the hypothesis that CCK-33 is a more effective stimulant of the hepatic proper vagal afferent nerves than CCK-8. In contrast to the results in H rats, the inhibitory potencies of both peptides were significantly and equivalently reduced in HGD rats compared with sham rats. This suggests that there is an inhibitory interaction between the stimulation of the gastroduodenal and hepatic proper afferent fibers by CCK-33.

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