Effects of δ-Conotoxins PVIA and SVIE on Sodium Channels in the Amphibian Sympathetic Nervous System

2005 ◽  
Vol 94 (6) ◽  
pp. 3916-3924 ◽  
Author(s):  
Peter J. West ◽  
Grzegorz Bulaj ◽  
Doju Yoshikami
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Sodium Channels ◽  
Time Course ◽  
Sympathetic Neurons ◽  
Leopard Frog ◽  
Dependent Manner ◽  
Cone Snail ◽  
Sodium Currents ◽  
Sympathetic Nervous

δ-Conotoxins are a family of small, disulfide-rich peptides found in the venoms of predatory cone snails ( Conus). We examined in detail the effects of δ-conotoxin PVIA from the fish hunting cone snail Conus purpurascens on sodium currents in dissociated sympathetic neurons from the leopard frog Rana pipiens. We also compared this toxin’s effects with those of δ-conotoxin SVIE from Conus striatus, another piscivorous cone snail. d-PVIA slowed the time-course of inactivation of δ sodium currents and shifted the voltage-dependence of activation and steady-state inactivation to more hyperpolarized potentials. Similar, albeit more pronounced, effects were seen with d-SVIE. While the effects of d-PVIA were reversed by washing, those of d-SVIE were largely irreversible over the time-course of these experiments. The effects of d-PVIA could be suppressed by conditioning depolarizations in a voltage- and time-dependent manner, whereas the effects of d-SVIE were largely resistant to conditioning depolarizations. Last, in intact sympathetic nervous system preparations, d-PVIA inhibited evoked trains of compound action potentials. Many of these effects of d-PVIA and d-SVIE are remarkably similar to those of toxins that bind to site 3 on voltage-gated sodium channels.

scholarly journals Local sympathetic neurons promote neutrophil egress from the bone marrow at the onset of acute inflammation

2020 ◽  
Vol 32 (11) ◽  
pp. 727-736 ◽  
Author(s):  
Tomoka Ao ◽  
Junichi Kikuta ◽  
Takao Sudo ◽  
Yutaka Uchida ◽  
Kenta Kobayashi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Immune Cells ◽  
Acute Inflammation ◽  
Sympathetic Neurons ◽  
Dependent Manner ◽  
Adrenergic Signaling ◽  
Sympathetic Nervous

Abstract The sympathetic nervous system plays critical roles in the differentiation, maturation and recruitment of immune cells under homeostatic conditions, and in responses to environmental stimuli, although its role in the migratory control of immune cells during acute inflammation remains unclear. In this study, using an advanced intravital bone imaging system established in our laboratory, we demonstrated that the sympathetic nervous system locally regulates neutrophil egress from the bone marrow for mobilization to inflammatory foci. We found that sympathetic neurons were located close to blood vessels in the bone marrow cavity; moreover, upon lipopolysaccharide (LPS) administration, local sympathectomy delayed neutrophil egress from the bone marrow and increased the proportion of neutrophils that remained in place. We also showed that vascular endothelial cells produced C-X-C motif chemokine ligand 1 (CXCL1), which is responsible for neutrophil egress out of the bone marrow. Its expression was up-regulated during acute inflammation, and was suppressed by β-adrenergic receptor blockade, which was accompanied with inhibition of neutrophil egress into the systemic circulation. Furthermore, systemic β-adrenergic signaling blockade decreased the recruitment of neutrophils in the lung under conditions of acute systemic inflammation. Taken together, the results of this study first suggested a new regulatory system, wherein local sympathetic nervous activation promoted neutrophil egress by enhancing Cxcl1 expression in bone marrow endothelial cells in a β-adrenergic signaling-dependent manner, contributing to the recruitment of neutrophils at the onset of inflammation in vivo.

Effects of exercise intensity and duration on norepinephrine spillover and clearance in humans

1993 ◽  
Vol 75 (2) ◽  
pp. 668-674 ◽  
Author(s):  
U. Leuenberger ◽  
L. Sinoway ◽  
S. Gubin ◽  
L. Gaul ◽  
D. Davis ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Exercise Intensity ◽  
Time Course ◽  
Work Load ◽  
Dynamic Exercise ◽  
High Exercise Intensity ◽  
Sympathetic Nervous ◽  
Young Subjects ◽  
Norepinephrine Spillover

During dynamic exercise, blood flow to exercising muscle is closely matched to metabolic demands. This is made possible by metabolic vasodilation, vasoconstriction in inactive vascular beds, and a rise in cardiac output. The sympathetic nervous system plays an important role in regulating this exercise response. In this study, we used steady-state infusions of tritiated norepinephrine ([3H]NE) to determine the magnitude and time course of the arterial NE spillover response to sustained upright bicycle exercise at low (n = 11) and moderate-to-high (n = 14) exercise intensity (25 and 65% of maximum work load, respectively) in normal young subjects. In addition, we sought to examine whether exercise was associated with a change in NE clearance. During 30 min of low-level exercise, arterial NE spillover increased from 1.45 +/- 0.13 to 3.14 +/- 0.30 nmol.min-1 x m-2 (P < 0.01) and appeared to plateau at 20–30 min of exercise; NE clearance remained unchanged. During 20 min of moderate-to-high-intensity exercise, we found a substantial and progressive rise of arterial NE spillover from 2.15 +/- 0.27 to 13.52 +/- 1.62 nmol.min-1 x m-2 (P < 0.01). NE clearance decreased from 0.91 +/- 0.05 to 0.80 +/- 0.05 l.min-1 x m-2 (P < 0.05). These data suggest that, during dynamic exercise, sympathetic nervous system activity is related to exercise intensity, and there appears to be an interaction between the effects of exercise intensity and duration on NE spillover. In addition, at moderate-to-high exercise intensity, a small decrease of NE clearance contributes to the rise in plasma NE.

scholarly journals Recording sympathetic nerve activity chronically in rats: surgery techniques, assessment of nerve activity, and quantification

2013 ◽  
Vol 305 (10) ◽  
pp. H1407-H1416 ◽  
Author(s):  
Sean D. Stocker ◽  
Martin S. Muntzel
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Sympathetic Nerve ◽  
Time Course ◽  
Sympathetic Nerve Activity ◽  
Surgical Approaches ◽  
Nerve Activity ◽  
Disease States ◽  
Nervous System Function ◽  
Sympathetic Nervous

The sympathetic nervous system plays a pivotal role in homeostasis through its direct innervation and functional impact on a variety of end organs. In rats, a number of methods are available to assess sympathetic nervous system function. Traditionally, direct recording of sympathetic nerve activity (SNA) has been restricted to acute, anesthetized preparations or conscious animals within a few days after electrode implantation. However, these approaches provide short-term data in studies designed to investigate changes in SNA during chronic disease states. Over the last several years, chronic SNA recording has been pioneered in rabbits and more recently in rats. The purpose of this article is to provide insights and a “how to” guide for chronic SNA recordings in rats based on experiences from two independent laboratories. We will present common methodologies used to chronically record SNA, characteristics and methods to distinguish sympathetic bursts versus electrical artifacts (and provide corresponding audio clips when available), and provide suggestions for analysis and presentation of data. In many instances, these same guidelines are applicable to acute SNA recordings. Using the surgical approaches described herein, both laboratories have been able to chronically record SNA in >50% of rats for a duration >3 wk. The ability to record SNA over the time course of several weeks will, undoubtedly, greatly impact the field of autonomic and cardiovascular physiology.

TH and NPY in sympathetic neurovascular cultures: role of LIF and NT-3

2008 ◽  
Vol 294 (1) ◽  
pp. C306-C312 ◽  
Author(s):  
Deborah H. Damon
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Vascular Function ◽  
Important Determinant ◽  
Sympathetic Neurons ◽  
Sympathetic Nerves ◽  
Sympathetic Control ◽  
Neurotrophin 3 ◽  
Sympathetic Nervous

The sympathetic nervous system is an important determinant of vascular function. The effects of the sympathetic nervous system are mediated via release of neurotransmitters and neuropeptides from postganglionic sympathetic neurons. The present study tests the hypothesis that vascular smooth muscle cells (VSM) maintain adrenergic neurotransmitter/neuropeptide expression in the postganglionic sympathetic neurons that innervate them. The effects of rat aortic and tail artery VSM (AVSM and TAVSM, respectively) on neuropeptide Y (NPY) and tyrosine hydroxylase (TH) were assessed in cultures of dissociated sympathetic neurons. AVSM decreased TH (39 ± 12% of control) but did not affect NPY. TAVSM decreased TH (76 ± 10% of control) but increased NPY (153 ± 20% of control). VSM expressed leukemia inhibitory factor (LIF) and neurotrophin-3 (NT-3), which are known to modulate NPY and TH expression. Sympathetic neurons innervating blood vessels expressed LIF and NT-3 receptors. Inhibition of LIF inhibited the effect of AVSM on TH. Inhibition of neurotrophin-3 (NT-3) decreased TH and NPY in neurons grown in the presence of TAVSM. These data suggest that vascular-derived LIF decreases TH and vascular-derived NT-3 increases or maintains NPY and TH expression in postganglionic sympathetic neurons. NPY and TH in vascular sympathetic nerves are likely to modulate NPY and/or norepinephrine release from these nerves and are thus likely to affect blood flow and blood pressure. The present studies suggest a novel mechanism whereby VSM would modulate sympathetic control of vascular function.

scholarly journals No Evidence of Neurogenesis in Adult Rat Sympathetic Ganglia Following Guanethidine-Induced Neuronal Loss

2019 ◽  
Vol 48 (1) ◽  
pp. 228-237 ◽  
Author(s):  
Karen M. Walters ◽  
Magalie Boucher ◽  
Germaine G. Boucher ◽  
Alan C. Opsahl ◽  
Peter R. Mouton ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Sympathetic Neurons ◽  
Neuronal Loss ◽  
Sympathetic Ganglia ◽  
Adult Rat ◽  
Unbiased Stereology ◽  
Neuron Density ◽  
Sympathetic Nervous ◽  
Cervical Ganglia

The potential for neurogenesis in the cranial (superior) cervical ganglia (SCG) of the sympathetic nervous system was evaluated. Eleven consecutive daily doses of guanethidine (100 mg/kg/d) were administered intraperitoneally to rats in order to destroy postganglionic sympathetic neurons in SCG. Following the last dose, animals were allowed to recover 1, 3, or 6 months. Right and left SCG from guanethidine-treated and age-matched, vehicle-treated control rats were harvested for histopathologic, morphometric, and stereologic evaluations. Both morphometric and stereologic evaluations confirmed neuron loss following guanethidine treatment. Morphometric analysis revealed a 50% to 60% lower number of tyrosine hydroxylase (TH)-positive neurons per unit area of SCG at both 3 and 6 months of recovery, compared to ganglia of age-matched controls, with no evidence of restoration of neuron density between 3 and 6 months. Reductions in TH-positive neurons following guanethidine treatment were corroborated by unbiased stereology of total hematoxylin and eosin-stained neuron numbers in SCG. Stereologic analyses revealed that total neuron counts were lower by 37% at 3 months of recovery when compared to age-matched vehicle controls, again with no obvious restoration between 3 and 6 months. Thus, no evidence was found that postganglionic neurons of the sympathetic nervous system in the adult rat have a neurogenic capacity.

Cloning and characterization of the sympathetic nervous system mutant, Sym3, in zebrafish

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9541-9541
Author(s):  
R. George ◽  
J. Lee ◽  
R. Stewart ◽  
T. Bayul ◽  
N. Campisi ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Sympathetic Neurons ◽  
Functional Characterization ◽  
Complementation Group ◽  
Sympathetic Ganglia ◽  
Zebrafish Model ◽  
Curly Tail ◽  
Sympathetic Nervous

9541 Background: Neuroblastoma (NB) is a neural crest tumor manifesting in the adrenal gland and the sympathetic ganglia. The goal of this project was to use the zebrafish model to identify genes involved in the development of the peripheral sympathetic nervous system (PSNS). We used the expression of tyrosine hydroxylase (TH) in the cervical sympathetic ganglion (cervical complex, CC), as a marker for PSNS development. TH expression can be observed by whole-mount RNA in situ hybridization in 2–3-day zebrafish embryos in the CC. Methods: In an ethyl nitrosourea mutagenesis screen for mutations that affect PSNS development, we identified a putative mutant, Sym3, showing a change in modeling of the TH staining cells in the region of the CC. Results and Conclusion: The TH-positive cells were scattered rather than conglomerated together as is typical of cells in the normal CC. The mutant was also characterized by a “curly-tail” phenotype. After the mutation was recovered from the F3 generation, heterozygous pairs harboring the mutation were identified. Using genome wide scanning PCR assay, linkage of the Sym3 mutation to microsatellite markers z9704 and z1351, located on Linkage Group 1, was established. Complementation assays were performed with other known “curly tail” mutants in the genetic interval, which revealed that Sym3 and a previously described vic mutant were in the same complementation group. The vic mutant is characterized by curved body axis, left to right asymmetry and kidney cysts and results from a mutation in the ARL13b gene, a protein of the Ras superfamily involved in intracellular trafficking and cilial motility. The vic mutation is a C to A transition at position 104 in the second exon of the open reading frame (T35L). The ARL13b gene in Sym3 has a four aa insertion at the 5’ end of the 4th exon of the coding region.The mutant Sym3 phenotype can be rescued by overexpression of the normal ARL13b gene. The vic mutant showed defective cilia formation in the kidney. However, immunocytochemistry showed normal cilia in the Sym3 mutant, suggesting that the Sym3 allele of ARL13b affects the development of alternative tissues during development, such as the aggregation of sympathetic neurons into discrete ganglia. Further functional characterization of the Sym3 mutation is ongoing. No significant financial relationships to disclose.

Maintenance of blood pressure by β adrenoceptor mediated renin release during different forms of anesthesia in rats

1981 ◽  
Vol 59 (4) ◽  
pp. 364-370 ◽  
Author(s):  
F. H. H. Leenen ◽  
A. P. Provoost
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Plasma Renin ◽  
Dependent Manner ◽  
Ether Anesthesia ◽  
Pentobarbital Anesthesia ◽  
Urethane Anesthesia ◽  
Sympathetic Nervous

In rats we assessed the role of the sympathetic nervous system in the increase of plasma renin activity (PRA) following induction of anesthesia by urethane, ether, or pentobarbital and the role of these increased levels of PRA in the maintenance of blood pressure.Urethane and ether induced marked, sustained increases in PRA. Pentobarbital was less effective in this regard. Propranolol inhibited the response of PRA to urethane and ether in a dose-dependent manner but not the renin response to pentobarbital. Similarly, neonatal sympathectomy with 6-hydroxydopamine together with removal of the adrenal medulla prevented the renin response to urethane but not to pentobarbital.Blood pressure changed only slightly during urethane anesthesia, showed a sustained decrease during ether anesthesia, and a gradual return to normal following a marked initial drop during pentobarbital anesthesia. Saralasin pretreatment induced a marked decrease (40–45 mmHg; 1 mmHg = 133.322 Pa) in blood pressure during urethane anesthesia and smaller (10–20 mmHg) additional decreases during ether and pentobarbital anesthesia. In contrast, propranolol pretreatment did not significantly affect blood pressure during ether anesthesia and affected it to a minor degree (by 10–15 mmHg) during urethane and pentobarbital anesthesia.The results indicate that the increases in PRA following induction of anesthesia by urethane or ether, but not by pentobarbital, are mediated through the peripheral sympathetic nervous system via β adrenoceptors. The rennin–angiotensin system appears to be essential for the maintenance of a normal blood pressure during urethane anesthesia but plays a less prominent role in this regard during ether and pentobarbital anesthesia. The propranolol studies suggest that the hypotensive effect of propranolol through blockade of the renin response during urethane- and ether-induced anesthesia is masked by a pressor effect of propranolol.

scholarly journals Neural regulation of hypoxia-inducible factors and redox state drives the pathogenesis of hypertension in a rodent model of sleep apnea

2015 ◽  
Vol 119 (10) ◽  
pp. 1152-1156 ◽  
Author(s):  
Gregg L. Semenza ◽  
Nanduri R. Prabhakar
Keyword(s):  
Nervous System ◽  
Sleep Apnea ◽  
Sympathetic Nervous System ◽  
Brain Stem ◽  
Carotid Body ◽  
Sympathetic Neurons ◽  
Ventrolateral Medulla ◽  
Obstructive Sleep ◽  
Sympathetic Nervous ◽  
The Brain

Obstructive sleep apnea (OSA) is one of the most common causes of hypertension in western societies. OSA causes chronic intermittent hypoxia (CIH) in specialized O2-sensing glomus cells of the carotid body. CIH generates increased reactive oxygen species (ROS) that trigger a feedforward mechanism in which increased intracellular calcium levels ([Ca2+]i) trigger increased HIF-1α synthesis and increased HIF-2α degradation. As a result, the normal homeostatic balance between HIF-1α-dependent prooxidant and HIF-2α-dependent antioxidant enzymes is disrupted, leading to further increases in ROS. Carotid body sensory nerves project to the nucleus tractus solitarii, from which the information is relayed via interneurons to the rostral ventrolateral medulla in the brain stem, which sends sympathetic neurons to the adrenal medulla to stimulate the release of epinephrine and norepinephrine, catecholamines that increase blood pressure. At each synapse, neurotransmitters trigger increased [Ca2+]i, HIF-1α:HIF-2α, and Nox2:Sod2 activity that generates increased ROS levels. These responses are not observed in other regions of the brain stem that do not receive input from the carotid body or signal to the sympathetic nervous system. Thus sympathetic nervous system homeostasis is dependent on a balance between HIF-1α and HIF-2α, disruption of which results in hypertension in OSA patients.

scholarly journals The Impact of α-Adrenoceptors in the Regulation of the Hypotonicity-Induced Increase in Duodenal Mucosal Permeability In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2096
Author(s):  
John Sedin ◽  
David Dahlgren ◽  
Markus Sjöblom ◽  
Olof Nylander
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Arterial Blood Pressure ◽  
Dependent Manner ◽  
Mucosal Permeability ◽  
Arterial Blood ◽  
Α2 Adrenoceptor ◽  
Sympathetic Nervous

The duodenal mucosa is regularly exposed to a low osmolality, and recent experiments suggest that hypotonicity increases mucosal permeability in an osmolality-dependent manner. The aim was to examine whether the sympathetic nervous system, via action on α-adrenoceptors, affects the hypotonicity-induced increase in duodenal mucosal permeability. The duodenum of anaesthetised rats was perfused in vivo with a 50 mM NaCl solution in the presence of adrenergic α-adrenoceptor drugs. Studied were the effects on mucosal permeability (blood-to-lumen clearance of 51Cr-EDTA), arterial blood pressure, luminal alkalinisation, transepithelial fluid flux, and motility. Hypotonicity induced a six-fold increase in mucosal permeability, a response that was reversible and repeatable. The α2-adrenoceptor agonist clonidine abolished the hypotonicity-induced increase in mucosal permeability, reduced arterial blood pressure, inhibited duodenal motility, and decreased luminal alkalinisation. The α2-adrenoceptor antagonists, yohimbine and idazoxan, prevented the inhibitory effect of clonidine on the hypotonicity-induced increase in mucosal permeability. The α1-agonist phenylephrine or the α1-antagonist prazosin elicited their predicted effect on blood pressure but did not affect the hypotonicity-induced increase in mucosal permeability. None of the α1- or α2-adrenoceptor drugs changed the hypotonicity-induced net fluid absorption. In conclusion, stimulation of the adrenergic α2-adrenoceptor prevents the hypotonicity-induced increase in mucosal permeability, suggesting that the sympathetic nervous system has the capability to regulate duodenal mucosal permeability.

scholarly journals The sympathetic nervous system stimulates anti-inflammatory B cells in collagen-type II-induced arthritis

2011 ◽  
Vol 71 (3) ◽  
pp. 432-439 ◽  
Author(s):  
Georg Pongratz ◽  
Madlen Melzer ◽  
Rainer H Straub
Keyword(s):  
Nervous System ◽  
B Cells ◽  
Sympathetic Nervous System ◽  
B Cell ◽  
Late Phase ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Sympathetic Nervous ◽  
Anti Inflammatory

BackgroundAs previously shown, the sympathetic nervous system (SNS) shows proinflammatory activity during initiation of arthritis but is anti-inflammatory in established collagen-induced arthritis (CIA). Interleukin 10 (IL-10)-producing B cells suppress arthritis and are a potential target of the SNS because (1) B cells express functional β2-adrenoceptors (β2ARs) and (2) IL-10, at least in monocytes/macrophages, is regulated in a cAMP/PKA/CREB-dependent manner.ObjectiveTo test the hypothesis that anti-inflammatory effects of the SNS in CIA are mediated by stimulating IL-10-producing anti-inflammatory B cells.MethodsCollagen-induced arthritis in DBA/1 mice, sympathectomy, adoptive B cell transfer, in vitro B cell culture, and assessment of B cell IL-10 production.Results and conclusionMice treated with B cells from SNS-intact mice showed less severe arthritis than mice treated with B cells from sympathectomised mice. This anti-inflammatory action of B cells from SNS-intact mice correlated with increased IL-10 produced by B cells, which was mediated by norepinephrine (NE), in a β2AR, PKA-dependent manner. However, an NE-mediated increase in IL-10 was seen only in B cells from immunised but not naive mice, explaining in part the anti-inflammatory properties of the SNS in the late phase of arthritis. Finally, animals treated with B cells isolated from immunised mice and activated in vitro in the presence of a β2AR stimulus showed a decrease in arthritis severity in comparison with controls, an approach that might be used for future cellular treatment strategies.

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