scholarly journals Ankyrin-G coordinates assembly of the spectrin-based membrane skeleton, voltage-gated sodium channels, and L1 CAMs at Purkinje neuron initial segments

2001 ◽  
Vol 155 (5) ◽  
pp. 739-746 ◽  
Author(s):  
Scott M. Jenkins ◽  
Vann Bennett
Keyword(s):  
Adhesion Molecules ◽  
Sodium Channels ◽  
Action Potentials ◽  
Membrane Skeleton ◽  
Purkinje Neuron ◽  
Voltage Gated ◽  
Ankyrin G ◽  
Voltage Gated Sodium Channels ◽  
Cerebellar Purkinje Neurons ◽  
Axon Initial Segments

The axon initial segment is an excitable membrane highly enriched in voltage-gated sodium channels that integrates neuronal inputs and initiates action potentials. This study identifies Nav1.6 as the voltage-gated sodium channel isoform at mature Purkinje neuron initial segments and reports an essential role for ankyrin-G in coordinating the physiological assembly of Nav1.6, βIV spectrin, and the L1 cell adhesion molecules (L1 CAMs) neurofascin and NrCAM at initial segments of cerebellar Purkinje neurons. Ankyrin-G and βIV spectrin appear at axon initial segments by postnatal day 2, whereas L1 CAMs and Nav1.6 are not fully assembled at continuous high density along axon initial segments until postnatal day 9. L1 CAMs and Nav1.6 therefore do not initiate protein assembly at initial segments. βIV spectrin, Nav1.6, and L1 CAMs are not clustered in adult Purkinje neuron initial segments of mice lacking cerebellar ankyrin-G. These results support the conclusion that ankyrin-G coordinates the physiological assembly of a protein complex containing transmembrane adhesion molecules, voltage-gated sodium channels, and the spectrin membrane skeleton at axon initial segments.

scholarly journals βIV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier

2002 ◽  
Vol 156 (2) ◽  
pp. 337-348 ◽  
Author(s):  
Masayuki Komada ◽  
Philippe Soriano
Keyword(s):  
Sodium Channels ◽  
Embryonic Stem ◽  
Nodes Of Ranvier ◽  
Gene Trapping ◽  
Voltage Gated ◽  
Ankyrin G ◽  
Membrane Cytoskeleton ◽  
Voltage Gated Sodium Channels ◽  
Axon Initial Segments ◽  
Sodium Channel Clustering

β-Spectrin and ankyrin are major components of the membrane cytoskeleton. We have generated mice carrying a null mutation in the βIV-spectrin gene using gene trapping in embryonic stem cells. Mice homozygous for the mutation exhibit tremors and contraction of hindlimbs. βIV-spectrin expression is mostly restricted to neurons, where it colocalizes with and binds to ankyrin-G at axon initial segments (AISs) and nodes of Ranvier (NR). In βIV-spectrin–null neurons, neither ankyrin-G nor voltage-gated sodium channels (VGSC) are correctly clustered at these sites, suggesting that impaired action potential caused by mislocalization of VGSC leads to the phenotype. Conversely, in ankyrin-G–null neurons, βIV-spectrin is not localized to these sites. These results indicate that βIV-spectrin and ankyrin-G mutually stabilize the membrane protein cluster and the linked membrane cytoskeleton at AIS and NR.

scholarly journals Action Potentials and Na+ voltage-gated ion channels in Placozoa

2020 ◽  
Author(s):  
Daria Y. Romanova ◽  
Ivan V. Smirnov ◽  
Mikhail A. Nikitin ◽  
Andrea B. Kohn ◽  
Alisa I. Borman ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Action Potentials ◽  
Parallel Evolution ◽  
Cell Types ◽  
List Type ◽  
Behavioral Integration ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Invertebrate Animal ◽  
Sodium Dependent

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

Voltage-gated sodium channels and pain

e-Neuroforum ◽  
2017 ◽  
Vol 23 (3) ◽  
Author(s):  
Carla Nau ◽  
Enrico Leipold
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sodium Channels ◽  
Action Potentials ◽  
Afferent Pathways ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
The Central Nervous System

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

scholarly journals Recording action potential propagation in single axons using multi-electrode arrays

2017 ◽  
Author(s):  
Kenneth R. Tovar ◽  
Daniel C. Bridges ◽  
Bian Wu ◽  
Connor Randall ◽  
Morgane Audouard ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Action Potential ◽  
Sodium Channels ◽  
Action Potentials ◽  
Extracellular Recording ◽  
Electrode Arrays ◽  
Action Potential Propagation ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Axonal Arbors

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.

scholarly journals The periodic axon membrane skeleton leads to high-density sodium nanodomains but does not impact action potentials

2021 ◽  
Author(s):  
Zhaojie Chai ◽  
Anastasios V. Tzingonunis ◽  
George Lykotrafitis
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Action Potentials ◽  
High Density ◽  
Homogeneous Distribution ◽  
Voltage Gated ◽  
Periodic Distribution ◽  
Voltage Gated Sodium Channels ◽  
The Impact ◽  
Periodic Arrangement

ABSTRACTRecent work has established that axons have a periodic skeleton structure comprising of azimuthal actin rings connected via longitudinal spectrin tetramer filaments. This structure endows the axon with structural integrity and mechanical stability. Additionally, voltage-gated sodium channels follow the periodicity of the active-spectrin arrangement, spaced ∼190 nm segments apart. The impact of this periodic sodium channel arrangement on the generation and propagation of action potentials is unknown. To address this question, we simulated an action potential using the Hodgkin-Huxley formalism in a cylindrical compartment but instead of using a homogeneous distribution of voltage-gated sodium channels in the membrane, we applied the experimentally determined periodic arrangement. We found that the periodic distribution of voltage-gated sodium channels does not significantly affect the generation or propagation of action potentials, but instead leads to high-density sodium channel nanodomains. This work provides a foundation for future studies investigating the role of the voltage-gated sodium channel periodic arrangement in the axon.

scholarly journals βIVΣ1 spectrin stabilizes the nodes of Ranvier and axon initial segments

2004 ◽  
Vol 166 (7) ◽  
pp. 983-990 ◽  
Author(s):  
Sandra Lacas-Gervais ◽  
Jun Guo ◽  
Nicola Strenzke ◽  
Eric Scarfone ◽  
Melanie Kolpe ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Actin Binding ◽  
Ultrastructural Changes ◽  
Nodes Of Ranvier ◽  
Ankyrin G ◽  
Voltage Gated Sodium Channels ◽  
Dense Membrane ◽  
Afferent Fibers ◽  
Actin Binding Domain ◽  
Axon Initial Segments

Saltatory electric conduction requires clustered voltage-gated sodium channels (VGSCs) at axon initial segments (AIS) and nodes of Ranvier (NR). A dense membrane undercoat is present at these sites, which is thought to be key for the focal accumulation of channels. Here, we prove that βIVΣ1 spectrin, the only βIV spectrin with an actin-binding domain, is an essential component of this coat. Specifically, βIVΣ1 coexists with βIVΣ6 at both AIS and NR, being the predominant spectrin at AIS. Removal of βIVΣ1 alone causes the disappearance of the nodal coat, an increased diameter of the NR, and the presence of dilations filled with organelles. Moreover, in myelinated cochlear afferent fibers, VGSC and ankyrin G clusters appear fragmented. These ultrastructural changes can explain the motor and auditory neuropathies present in βIVΣ1 −/− mice and point to the βIVΣ1 spectrin isoform as a master-stabilizing factor of AIS/NR membranes.

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