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.

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.

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 High glucose increases action potential firing of catecholamine neurons in the nucleus of the solitary tract by increasing spontaneous glutamate inputs

2017 ◽  
Vol 313 (3) ◽  
pp. R229-R239 ◽  
Author(s):  
Brandon L. Roberts ◽  
Mingyan Zhu ◽  
Huan Zhao ◽  
Crystal Dillon ◽  
Suzanne M. Appleyard
Keyword(s):  
Action Potential ◽  
Glucose Concentration ◽  
Glutamate Release ◽  
Cardiovascular Reflexes ◽  
Solitary Tract ◽  
Action Potential Firing ◽  
Nodose Ganglia ◽  
Potential Firing ◽  
Low Glucose ◽  
The Brain

Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brain stem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal, and stress. However, it is not known if they respond to changes in glucose. Here we determined whether NTS-CA neurons respond to changes in glucose concentration and the mechanism involved. We found that decreasing glucose concentrations from 5 mM to 2 mM to 1 mM, significantly decreased action potential firing in a cell-attached preparation, whereas increasing it back to 5 mM increased the firing rate. This effect was dependent on glutamate release from afferent terminals and required presynaptic 5-HT3Rs. Decreasing the glucose concentration also decreased both basal and 5-HT3R agonist-induced increase in the frequency of spontaneous glutamate inputs onto NTS-CA neurons. Low glucose also blunted 5-HT-induced inward currents in nodose ganglia neurons, which are the cell bodies of vagal afferents. The effect of low glucose in both nodose ganglia cells and in NTS slices was mimicked by the glucokinase inhibitor glucosamine. This study suggests that NTS-CA neurons are glucosensing through a presynaptic mechanism that is dependent on vagal glutamate release, 5-HT3R activity, and glucokinase.

scholarly journals What is transmitted in “synaptic transmission”?

2010 ◽  
Vol 34 (2) ◽  
pp. 115-116 ◽  
Author(s):  
Erik Montagna ◽  
Adriana M. S. de Azevedo ◽  
Camilla Romano ◽  
Ronald Ranvaud
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Presynaptic Terminal ◽  
Synaptic Integration ◽  
High Grade ◽  
Transmission Right ◽  
The Mind

Even students that obtain a high grade in neurophysiology often carry away a serious misconception concerning the final result of the complex set of events that follows the arrival of an action potential at the presynaptic terminal. The misconception consists in considering that “at a synapse, information is passed on from one neuron to the next” is equivalent to (and often expressed explicitly as) “the action potential passes from one neuron to the next.” More than half of four groups of students who were asked to comment on an excerpt from a recent physiology textbook that openly stated the misconception had no clear objection to the text presented. We propose that the first culprit in generating this misconception is the term “synaptic transmission,” which promotes the notion of transferring something or passing something along (implicitly unchanged). To avoid establishing this misconception, the first simple suggestion is to use words like “synaptic integration” rather than “synaptic transmission” right from the start. More generally, it would be important to focus on the function of synaptic events rather than on rote listing of all the numerous steps that are known to occur, which are so complex as to saturate the mind of the student.

scholarly journals Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents

2013 ◽  
Vol 304 (10) ◽  
pp. G908-G916 ◽  
Author(s):  
Shizhong Zhang ◽  
Gintautas Grabauskas ◽  
Xiaoyin Wu ◽  
Moon Kyung Joo ◽  
Andrea Heldsinger ◽  
...  
Keyword(s):  
Mast Cell ◽  
Action Potential ◽  
Cell Activation ◽  
Vagal Afferents ◽  
Mast Cell Activation ◽  
Lipid Mediator ◽  
Prostaglandin D2 ◽  
Patch Clamp Recording ◽  
C Fibers ◽  
Ganglion Neurons

Sensitization of esophageal afferents plays an important role in esophageal nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases the preformed mediators histamine and tryptase, which play important roles in sensitization of esophageal vagal nociceptive C fibers. PGD2 is a lipid mediator released by activated MCs. Whether PGD2 plays a role in this sensitization process has yet to be determined. Expression of the PGD2 DP1 and DP2 receptors in nodose ganglion neurons was determined by immunofluorescence staining, Western blotting, and RT-PCR. Extracellular recordings were performed in ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal distension were compared before and after perfusion of PGD2, DP1 and DP2 receptor agonists, and MC activation, with or without pretreatment with antagonists. The effect of PGD2 on 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal nodose neurons was determined by patch-clamp recording. Our results demonstrate that DP1 and DP2 receptor mRNA and protein were expressed mainly in small- and medium-diameter neurons in nodose ganglia. PGD2 significantly increased esophageal distension-evoked action potential discharges in esophageal nodose C fibers. The DP1 receptor agonist BW 245C mimicked this effect. PGD2 directly sensitized DiI-labeled esophageal nodose neurons by decreasing the action potential threshold. Pretreatment with the DP1 receptor antagonist BW A868C significantly inhibited PGD2 perfusion- or MC activation-induced increases in esophageal distension-evoked action potential discharges in esophageal nodose C fibers. In conclusion, PGD2 plays an important role in MC activation-induced sensitization of esophageal nodose C fibers. This adds a novel mechanism of visceral afferent sensitization.

scholarly journals The role of Ca2+ in the protoveratrine-induced release of γ-aminobutyrate from rat brain slices

1980 ◽  
Vol 190 (2) ◽  
pp. 333-339 ◽  
Author(s):  
M C W Minchin
Keyword(s):  
Cerebral Cortex ◽  
Rat Brain ◽  
Dose Response ◽  
Transmitter Release ◽  
Response Curve ◽  
Brain Slices ◽  
Veratrum Alkaloids ◽  
Similar Dose ◽  
22Na Uptake

1. Protoveratrine A increased the release of gamma-amino[3H]butyrate from small slices of rat cerebral cortex. This effect increased with increasing protoveratrine concentration, reaching a maximum at 100 microM. 2. Removal of Ca2+ from the superfusing medium did not change the increase in release due to 10 microM-protoveratrine; however, the Ca2+ antagonists, compound D-600, La3+, Mn2+, Mg2+ and also high Ca2+ concentration inhibited the effect of the alkaloid, as did procaine. 3. Protoveratrine A increased the uptake of 22Na+ into the slices with a similar dose-response curve to that found for gamma-aminobutyrate release. For the most part, the substances that inhibited protoveratrine-stimulated gamma-aminobutyrate release also inhibited 22Na+ uptake, although the correlation was not perfect. 4. Although extracellular Ca2+ is not required for protoveratrine-induced gamma-aminobutyrate release, an increase in Na+ influx that is susceptible to inhibition by some Ca2+ antagonists does appear to be associated with this phenomenon. However, the possibility remains that changes in the free intracellular Ca2+ concentration may be important for transmitter release induced by depolarizing veratrum alkaloids.

CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents

2005 ◽  
Vol 289 (3) ◽  
pp. R695-R703 ◽  
Author(s):  
E. H. E. M. van de Wall ◽  
P. Duffy ◽  
R. C. Ritter
Keyword(s):  
Vagal Afferents ◽  
Gastric Distension ◽  
Solitary Tract ◽  
C Fibers ◽  
Balloon Distension ◽  
Electrophysiological Responses ◽  
Vagal Afferent ◽  
Fos Expression ◽  
Afferent Response ◽  
And Control

Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhances behavioral and electrophysiological responses to gastric distension in rats and people, we hypothesized that CCK might enhance the vagal afferent response to gastric distension via an action on capsaicin-insensitive vagal afferents. To test this hypothesis, we quantified expression of Fos-like immunoreactivity (Fos) in the dorsal vagal complex (DVC) of capsaicin-treated (Cap) and control rats (Veh), following gastric balloon distension alone and in combination with CCK injection. In Veh rats, intraperitoneal CCK significantly increased DVC Fos, especially in nucleus of the solitary tract (NTS), whereas in Cap rats, CCK did not significantly increase DVC Fos. In contrast to CCK, gastric distension did significantly increase Fos expression in the NTS of both Veh and Cap rats, although distension-induced Fos was attenuated in Cap rats. When CCK was administered during gastric distension, it significantly enhanced NTS Fos expression in response to distension in Cap rats. Furthermore, CCK's enhancement of distension-induced Fos in Cap rats was reversed by the selective CCK-A receptor antagonist lorglumide. We conclude that CCK directly activates capsaicin-sensitive C-type vagal afferents. However, in capsaicin-resistant A-type afferents, CCK's principal action may be facilitation of responses to gastric distension.

The effect of repetitive stimulation on the passive electrical properties of the presynaptic terminal of the squid giant synapse

1979 ◽  
Vol 206 (1164) ◽  
pp. 293-306 ◽  
Keyword(s):  
Electrical Properties ◽  
Transmitter Release ◽  
Sea Water ◽  
Presynaptic Terminal ◽  
Repetitive Stimulation ◽  
Constant Current ◽  
Current Pulses ◽  
Squid Giant Synapse ◽  
Giant Synapse ◽  
Passive Electrical Properties

The resting electrical properties of the presynaptic terminal of the squid giant synapse have been determined by using constant current pulses. After short periods of repetitive stimulation, the terminal resistance, time constant and capacitance are found to be increased. These changes are absent in terminals bathed in artificial sea water containing no calcium, and sea water containing 5 mM cobalt. It seems likely that these changes are associated with transmitter release.

scholarly journals Calcium-induced calcium release activates spontaneous miniature outward currents in newt medullary reticular formation neurons

2018 ◽  
Vol 120 (6) ◽  
pp. 3140-3154 ◽  
Author(s):  
Daniel B. Yaeger ◽  
Emma J. Coddington
Keyword(s):  
Action Potential ◽  
Reticular Formation ◽  
Calcium Release ◽  
Motor Behavior ◽  
Brain Slices ◽  
Medullary Reticular Formation ◽  
Outward Currents ◽  
Decay Times ◽  
Action Potential Threshold ◽  
Potential Threshold

Neurons in the medullary reticular formation are involved in the control of postural and locomotor behaviors in all vertebrates. Reticulospinal neurons in this brain region provide one of the major descending projections to the spinal cord. Although neurons in the newt medullary reticular formation have been extensively studied using in vivo extracellular recordings, little is known of their intrinsic biophysical properties or of the underlying circuitry of this region. Using whole cell patch-clamp recordings in brain slices containing the rostromedial reticular formation from adult male newts, we observed spontaneous miniature outward currents (SMOCs) in ~2/3 of neurons. Although SMOCs superficially resembled inhibitory postsynaptic currents (IPSCs), they had slower risetimes and decay times than spontaneous IPSCs. SMOCs required intracellular Ca2+ release from ryanodine receptors and were also dependent on the influx of extracellular Ca2+. SMOCs were unaffected by apamin but were partially blocked by iberiotoxin and charybdotoxin, indicating that SMOCs were mediated by big-conductance Ca2+-activated K+ channels. Application of the sarco/endoplasmic Ca2+ ATPase inhibitor cyclopiazonic acid blocked the generation of SMOCs and also increased neural excitability. Neurons with SMOCs had significantly broader action potentials, slower membrane time constants, and higher input resistance than neurons without SMOCs. Thus, SMOCs may serve as a mechanism to regulate action potential threshold in a majority of neurons within the newt medullary reticular formation. NEW & NOTEWORTHY The medullary reticular formation exerts a powerful influence on sensorimotor integration and subsequent motor behavior, yet little is known about the neurons involved. In this study, we identify a transient potassium current that regulates action potential threshold in a majority of medullary reticular neurons.

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