Voltage-gated sodium channels and pain

e-Neuroforum ◽  
2017 ◽  
Vol 23 (3) ◽  
Author(s):  
Carla Nau ◽  
Enrico Leipold

AbstractPainful stimuli are detected by specialized neurons, nociceptors, and are translated into action potentials, that are conducted along afferent pathways into the central nervous system, where they are conceived as pain. Voltage-gated sodium channels (Na

2017 ◽  
Author(s):  
Kenneth R. Tovar ◽  
Daniel C. Bridges ◽  
Bian Wu ◽  
Connor Randall ◽  
Morgane Audouard ◽  
...  

AbstractThe small caliber of central nervous system (CNS) axons makes routine study of axonal physiology relatively difficult. However, while recording extracellular action potentials from neurons cultured on planer multi-electrode arrays (MEAs) we found activity among groups of electrodes consistent with action potential propagation in single neurons. Action potential propagation was evident as widespread, repetitive cooccurrence of extracellular action potentials (eAPs) among groups of electrodes. These eAPs occurred with invariant sequences and inter-electrode latencies that were consistent with reported measures of action potential propagation in unmyelinated axons. Within co-active electrode groups, the inter-electrode eAP latencies were temperature sensitive, as expected for action potential propagation. Our data are consistent with these signals primarily reflecting axonal action potential propagation, from axons with a high density of voltage-gated sodium channels. Repeated codetection of eAPs by multiple electrodes confirmed these eAPs are from individual neurons and averaging these eAPs revealed sub-threshold events at other electrodes. The sequence of electrodes at which eAPs co-occur uniquely identifies these neurons, allowing us to monitor spiking of single identified neurons within neuronal ensembles. We recorded dynamic changes in single axon physiology such as simultaneous increases and decreases in excitability in different portions of single axonal arbors over several hours. Over several weeks, we measured changes in inter-electrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. We recorded action potential propagation signals in human induced pluripotent stem cell-derived neurons which could thus be used to study axonal physiology in human disease models.Significance StatementStudying the physiology of central nervous system axons is limited by the technical challenges of recording from axons with pairs of patch or extracellular electrodes at two places along single axons. We studied action potential propagation in single axonal arbors with extracellular recording with multi-electrode arrays. These recordings were non-invasive and were done from several sites of small caliber axons and branches. Unlike conventional extracellular recording, we unambiguously identified and labelled the neuronal source of propagating action potentials. We manipulated and quantified action potential propagation and found a surprisingly high density of axonal voltage-gated sodium channels. Our experiments also demonstrate that the excitability of different portions of axonal arbors can be independently regulated on time scales from hours to weeks.


Author(s):  
Paul G. DeCaen ◽  
Alfred L. George ◽  
Christopher H. Thompson

This chapter presents information about the structure, function, and molecular genetics of voltage-gated sodium channels expressed in the central nervous system. Sodium channels are essential for the generation and propagation of neuronal action potentials. Recent advances in structural biology have provided atomic-scale descriptions of sodium channel structure that can be related to specific functional properties. We further discuss cellular and subcellular localization, as well as the primary physiological functions mediated by sodium channels within the central nervous system. Finally, this chapter examines the association of various sodium channel isoforms with common brain disorders, including epilepsy, autism, and migraine, and explains the range of functional consequences of disease-associated mutations that are correlated with diverse human phenotypes.


Author(s):  
Monika Equit ◽  
Justine Niemczyk ◽  
Anna Kluth ◽  
Carla Thomas ◽  
Mathias Rubly ◽  
...  

Abstract. Objective: Fecal incontinence and constipation are common disorders in childhood. The enteric nervous system and the central nervous system are highly interactive along the brain-gut axis. The interaction is mainly afferent. These afferent pathways include centers that are involved in the central nervous processing of emotions as the mid/posterior insula and the anterior cingulate cortex. A previous study revealed altered processing of emotions in children with fecal incontinence. The present study replicates these results. Methods: In order to analyze the processing of emotions, we compared the event-related potentials of 25 children with fecal incontinence and constipation to those of 15 control children during the presentation of positive, negative, and neutral pictures. Results: Children with fecal incontinence and constipation showed altered processing of emotions, especially in the parietal and central cortical regions. Conclusions: The main study results of the previous study were replicated, increasing the certainty and validity of the findings.


1952 ◽  
Vol 15 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Orlando Aidar ◽  
William A. Geohegan ◽  
Luise H. Ungewitter

2013 ◽  
Vol 109 (7) ◽  
pp. 1775-1781 ◽  
Author(s):  
Paul Nardelli ◽  
Jaffar Khan ◽  
Randall Powers ◽  
Tim C. Cope ◽  
Mark M. Rich

Many critically ill patients in intensive care units suffer from an infection-induced whole body inflammatory state known as sepsis, which causes severe weakness in patients who survive. The mechanisms by which sepsis triggers intensive care unit-acquired weakness (ICUAW) remain unclear. Currently, research into ICUAW is focused on dysfunction of the peripheral nervous system. During electromyographic studies of patients with ICUAW, we noticed that recruitment was limited to few motor units, which fired at low rates. The reduction in motor unit rate modulation suggested that functional impairment within the central nervous system contributes to ICUAW. To understand better the mechanism underlying reduced firing motor unit firing rates, we moved to the rat cecal ligation and puncture model of sepsis. In isoflurane-anesthetized rats, we studied the response of spinal motoneurons to injected current to determine their capacity for initiating and firing action potentials repetitively. Properties of single action potentials and passive membrane properties of motoneurons from septic rats were normal, suggesting excitability was normal. However, motoneurons exhibited striking dysfunction during repetitive firing. The sustained firing that underlies normal motor unit activity and smooth force generation was slower, more erratic, and often intermittent in septic rats. Our data are the first to suggest that reduced excitability of neurons within the central nervous system may contribute to ICUAW.


2003 ◽  
Vol 26 (3) ◽  
pp. 209-224 ◽  
Author(s):  
Rafael Luján ◽  
Carlos de Cabo de la Vega ◽  
Eduardo Dominguez del Toro ◽  
Juan J Ballesta ◽  
Manuel Criado ◽  
...  

2020 ◽  
Vol 18 (10) ◽  
pp. 936-965
Author(s):  
Xuechao Hao ◽  
Mengchan Ou ◽  
Donghang Zhang ◽  
Wenling Zhao ◽  
Yaoxin Yang ◽  
...  

General anesthetics are a class of drugs that target the central nervous system and are widely used for various medical procedures. General anesthetics produce many behavioral changes required for clinical intervention, including amnesia, hypnosis, analgesia, and immobility; while they may also induce side effects like respiration and cardiovascular depressions. Understanding the mechanism of general anesthesia is essential for the development of selective general anesthetics which can preserve wanted pharmacological actions and exclude the side effects and underlying neural toxicities. However, the exact mechanism of how general anesthetics work is still elusive. Various molecular targets have been identified as specific targets for general anesthetics. Among these molecular targets, ion channels are the most principal category, including ligand-gated ionotropic receptors like γ-aminobutyric acid, glutamate and acetylcholine receptors, voltage-gated ion channels like voltage-gated sodium channel, calcium channel and potassium channels, and some second massager coupled channels. For neural functions of the central nervous system, synaptic transmission is the main procedure for which information is transmitted between neurons through brain regions, and intact synaptic function is fundamentally important for almost all the nervous functions, including consciousness, memory, and cognition. Therefore, it is important to understand the effects of general anesthetics on synaptic transmission via modulations of specific ion channels and relevant molecular targets, which can lead to the development of safer general anesthetics with selective actions. The present review will summarize the effects of various general anesthetics on synaptic transmissions and plasticity.


2020 ◽  
Author(s):  
Daria Y. Romanova ◽  
Ivan V. Smirnov ◽  
Mikhail A. Nikitin ◽  
Andrea B. Kohn ◽  
Alisa I. Borman ◽  
...  

AbstractPlacozoa are small disc-shaped animals, representing the simplest known, possibly ancestral, organization of free-living animals. With only six morphological distinct cell types, without any recognized neurons or muscle, placozoans exhibit fast effector reactions and complex behaviors. However, little is known about electrogenic mechanisms in these animals. Here, we showed the presence of rapid action potentials in four species of placozoans (Trichoplax adhaerens [H1 haplotype], Trichoplax sp.[H2], Hoilungia hongkongensis [H13], and Hoilungia sp. [H4]). These action potentials are sodium-dependent and can be inducible. The molecular analysis suggests the presence of 5-7 different types of voltage-gated sodium channels, which showed substantial evolutionary radiation compared to many other metazoans. Such unexpected diversity of sodium channels in early-branched animal lineages reflect both duplication events and parallel evolution of unique behavioral integration in these nerveless animals.HighlightsPlacozoans are the simplest known animals without recognized neurons and musclesWith only six morphological cell types, placozoans showed complex & rapid behaviorsSodium-dependent action potentials have been discovered in intact animalsVoltage-gated sodium channels (Nav) in Placozoa support a rapid behavioral integrationPlacozoans have more Nav channels that any studied invertebrate animal so farDiversification of Nav-channels highlight the unique evolution of these nerveless animals


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