scholarly journals Na+ channels get anchored…with a little help

2008 ◽  
Vol 183 (6) ◽  
pp. 975-977 ◽  
Author(s):  
Matthew N. Rasband
Keyword(s):  
Action Potentials ◽  
Na Channel ◽  
Na Channels ◽  
Nodes Of Ranvier ◽  
Ankyrin G ◽  
New Findings ◽  
Specific Accumulation ◽  
Channel Interactions ◽  
Kinase Ck2 ◽  
Axon Initial Segments

Neurons have high densities of voltage-gated Na+ channels that are restricted to axon initial segments and nodes of Ranvier, where they are responsible for initiating and propagating action potentials. New findings (Bréchet, A., M.-P. Fache, A. Brachet, G. Ferracci, A. Baude, M. Irondelle, S. Pereira, C. Leterrier, and B. Dargent. 2008. J. Cell Biol. 183:1101–1114) reveal that phosphorylation of several key serine residues by the protein kinase CK2 regulates Na+ channel interactions with ankyrin G. The presence of CK2 at the axon initial segment and nodes of Ranvier provides a mechanism to regulate the specific accumulation and retention of Na+ channels within these important domains.

scholarly journals βIV spectrin is recruited to axon initial segments and nodes of Ranvier by ankyrinG

2007 ◽  
Vol 176 (4) ◽  
pp. 509-519 ◽  
Author(s):  
Yang Yang ◽  
Yasuhiro Ogawa ◽  
Kristian L. Hedstrom ◽  
Matthew N. Rasband
Keyword(s):  
Ion Channels ◽  
Action Potentials ◽  
Dominant Negative ◽  
Protein Domain ◽  
Na Channel ◽  
Scaffolding Proteins ◽  
Membrane Domains ◽  
Nodes Of Ranvier ◽  
Transgene Delivery ◽  
Axon Initial Segments

High densities of ion channels at axon initial segments (AISs) and nodes of Ranvier are required for initiation, propagation, and modulation of action potentials in axons. The organization of these membrane domains depends on a specialized cytoskeleton consisting of two submembranous cytoskeletal and scaffolding proteins, ankyrinG (ankG) and βIV spectrin. However, it is not known which of these proteins is the principal organizer, or if the mechanisms governing formation of the cytoskeleton at the AIS also apply to nodes. We identify a distinct protein domain in βIV spectrin required for its localization to the AIS, and show that this domain mediates βIV spectrin's interaction with ankG. Dominant-negative ankG disrupts βIV spectrin localization, but does not alter endogenous ankG or Na+ channel clustering at the AIS. Finally, using adenovirus for transgene delivery into myelinated neurons, we demonstrate that βIV spectrin recruitment to nodes of Ranvier also depends on binding to ankG.

scholarly journals Nodes of Ranvier and axon initial segments are ankyrin G–dependent domains that assemble by distinct mechanisms

2007 ◽  
Vol 177 (5) ◽  
pp. 857-870 ◽  
Author(s):  
Yulia Dzhashiashvili ◽  
Yanqing Zhang ◽  
Jolanta Galinska ◽  
Isabel Lam ◽  
Martin Grumet ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Sodium Channels ◽  
Cytoskeletal Proteins ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Nodes Of Ranvier ◽  
Ankyrin G ◽  
Sites Of Action ◽  
Axon Initial Segments ◽  
Inside Out

Axon initial segments (AISs) and nodes of Ranvier are sites of action potential generation and propagation, respectively. Both domains are enriched in sodium channels complexed with adhesion molecules (neurofascin [NF] 186 and NrCAM) and cytoskeletal proteins (ankyrin G and βIV spectrin). We show that the AIS and peripheral nervous system (PNS) nodes both require ankyrin G but assemble by distinct mechanisms. The AIS is intrinsically specified; it forms independent of NF186, which is targeted to this site via intracellular interactions that require ankyrin G. In contrast, NF186 is targeted to the node, and independently cleared from the internode, by interactions of its ectodomain with myelinating Schwann cells. NF186 is critical for and initiates PNS node assembly by recruiting ankyrin G, which is required for the localization of sodium channels and the entire nodal complex. Thus, initial segments assemble from the inside out driven by the intrinsic accumulation of ankyrin G, whereas PNS nodes assemble from the outside in, specified by Schwann cells, which direct the NF186-dependent recruitment of ankyrin G.

Electrophysiological analysis of the neurotoxic action of a funnel-web spider toxin, delta-atracotoxin-HV1a, on insect voltage-gated Na+ channels

2001 ◽  
Vol 204 (4) ◽  
pp. 711-721 ◽  
Author(s):  
F. Grolleau ◽  
M. Stankiewicz ◽  
L. Birinyi-Strachan ◽  
X.H. Wang ◽  
G.M. Nicholson ◽  
...  
Keyword(s):  
Voltage Clamp ◽  
Action Potentials ◽  
Periplaneta Americana ◽  
Repetitive Firing ◽  
Na Channel ◽  
Na Channels ◽  
Patch Clamp Technique ◽  
Voltage Gated ◽  
Web Spider ◽  
Channel Inactivation

The effects of delta-ACTX-Hv1a, purified from the venom of the funnel-web spider Hadronyche versuta, were studied on the isolated giant axon and dorsal unpaired median (DUM) neurones of the cockroach Periplaneta americana under current- and voltage-clamp conditions using the double oil-gap technique for single axons and the patch-clamp technique for neurones. In parallel, the effects of the toxin were investigated on the excitability of rat dorsal root ganglion (DRG) neurones. In both DRG and DUM neurones, delta-ACTX-Hv1a induced spontaneous repetitive firing accompanied by plateau potentials. However, in the case of DUM neurones, plateau action potentials were facilitated when the membrane was artificially hyperpolarized. In cockroach giant axons, delta-ACTX-Hv1a also produced plateau action potentials, but only when the membrane was pre-treated with 3–4 diaminopyridine. Under voltage-clamp conditions, delta-ACTX-Hv1a specifically affected voltage-gated Na+ channels in both axons and DUM neurones. Both the current/voltage and conductance/voltage curves of the delta-ACTX-Hv1a-modified inward current were shifted 10 mV to the left of control curves. In the presence of delta-ACTX-Hv1a, steady-state Na+ channel inactivation became incomplete, causing the appearance of a non-inactivating component at potentials more positive than −40 mV. The amplitude of this non-inactivating component was dependent on the holding potential. From this study, it is concluded that, in insect neurones, delta-ACTX-Hv1a mainly affects Na+ channel inactivation by a mechanism that differs slightly from that of scorpion alpha-toxins.

scholarly journals Action potentials in Xenopus oocytes triggered by blue light

2020 ◽  
Vol 152 (5) ◽  
Author(s):  
Florian Walther ◽  
Dominic Feind ◽  
Christian vom Dahl ◽  
Christoph Emanuel Müller ◽  
Taulant Kukaj ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Blue Light ◽  
Action Potentials ◽  
Xenopus Oocytes ◽  
Na Channel ◽  
Xenopus Laevis Oocytes ◽  
Na Channels ◽  
Excitable Cells ◽  
Voltage Gated

Voltage-gated sodium (Na+) channels are responsible for the fast upstroke of the action potential of excitable cells. The different α subunits of Na+ channels respond to brief membrane depolarizations above a threshold level by undergoing conformational changes that result in the opening of the pore and a subsequent inward flux of Na+. Physiologically, these initial membrane depolarizations are caused by other ion channels that are activated by a variety of stimuli such as mechanical stretch, temperature changes, and various ligands. In the present study, we developed an optogenetic approach to activate Na+ channels and elicit action potentials in Xenopus laevis oocytes. All recordings were performed by the two-microelectrode technique. We first coupled channelrhodopsin-2 (ChR2), a light-sensitive ion channel of the green alga Chlamydomonas reinhardtii, to the auxiliary β1 subunit of voltage-gated Na+ channels. The resulting fusion construct, β1-ChR2, retained the ability to modulate Na+ channel kinetics and generate photosensitive inward currents. Stimulation of Xenopus oocytes coexpressing the skeletal muscle Na+ channel Nav1.4 and β1-ChR2 with 25-ms lasting blue-light pulses resulted in rapid alterations of the membrane potential strongly resembling typical action potentials of excitable cells. Blocking Nav1.4 with tetrodotoxin prevented the fast upstroke and the reversal of the membrane potential. Coexpression of the voltage-gated K+ channel Kv2.1 facilitated action potential repolarization considerably. Light-induced action potentials were also obtained by coexpressing β1-ChR2 with either the neuronal Na+ channel Nav1.2 or the cardiac-specific isoform Nav1.5. Potential applications of this novel optogenetic tool are discussed.

scholarly journals Perlecan is recruited by dystroglycan to nodes of Ranvier and binds the clustering molecule gliomedin

2015 ◽  
Vol 208 (3) ◽  
pp. 313-329 ◽  
Author(s):  
Cristina Colombelli ◽  
Marilena Palmisano ◽  
Yael Eshed-Eisenbach ◽  
Desirée Zambroni ◽  
Ernesto Pavoni ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Basal Lamina ◽  
Node Of Ranvier ◽  
Na Channel ◽  
Na Channels ◽  
Nodes Of Ranvier ◽  
Neural Conduction ◽  
Matrix Components ◽  
Selective Accumulation

Fast neural conduction requires accumulation of Na+ channels at nodes of Ranvier. Dedicated adhesion molecules on myelinating cells and axons govern node organization. Among those, specific laminins and dystroglycan complexes contribute to Na+ channel clustering at peripheral nodes by unknown mechanisms. We show that in addition to facing the basal lamina, dystroglycan is found near the nodal matrix around axons, binds matrix components, and participates in initial events of nodogenesis. We identify the dystroglycan-ligand perlecan as a novel nodal component and show that dystroglycan is required for the selective accumulation of perlecan at nodes. Perlecan binds the clustering molecule gliomedin and enhances clustering of node of Ranvier components. These data show that proteoglycans have specific roles in peripheral nodes and indicate that peripheral and central axons use similar strategies but different molecules to form nodes of Ranvier. Further, our data indicate that dystroglycan binds free matrix that is not organized in a basal lamina.

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.

scholarly journals β spectrin-dependent and domain specific mechanisms for Na+ channel clustering

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Cheng-Hsin Liu ◽  
Ryan Seo ◽  
Tammy Szu-Yu Ho ◽  
Michael Stankewich ◽  
Peter J Mohler ◽  
...  
Keyword(s):  
Nervous System ◽  
Motor Impairment ◽  
Cytoskeletal Proteins ◽  
System Structure ◽  
Na Channel ◽  
Na Channels ◽  
Domain Specific ◽  
Nervous System Function ◽  
Axon Initial Segments

Previously, we showed that a hierarchy of spectrin cytoskeletal proteins maintains nodal Na+ channels (Liu et al., 2020). Here, using mice lacking β1, β4, or β1/β4 spectrins, we show this hierarchy does not function at axon initial segments (AIS). Although β1 spectrin, together with AnkyrinR (AnkR), compensates for loss of nodal β4 spectrin, it cannot compensate at AIS. We show AnkR lacks the domain necessary for AIS localization. Whereas loss of β4 spectrin causes motor impairment and disrupts AIS, loss of β1 spectrin has no discernable effect on central nervous system structure or function. However, mice lacking both neuronal β1 and β4 spectrin show exacerbated nervous system dysfunction compared to mice lacking β1 or β4 spectrin alone, including profound disruption of AIS Na+ channel clustering, progressive loss of nodal Na+ channels, and seizures. These results further define the important role of AIS and nodal spectrins for nervous system function.

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