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 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.

Three-Dimensional Reconstruction of a Node of Ranvier Obtained by Serial Section Electron Tomography

2000 ◽  
Vol 6 (S2) ◽  
pp. 866-867
Author(s):  
G. Sosinsky ◽  
T. Deerinck ◽  
R. Greco ◽  
M. Ellisman
Keyword(s):  
Action Potentials ◽  
Electron Tomography ◽  
Three Dimensional ◽  
Node Of Ranvier ◽  
Na Channel ◽  
Nodes Of Ranvier ◽  
Myelinated Axons ◽  
Axonal Diameter ◽  
Dimensional Reconstruction ◽  
Section Electron

Nodes of Ranvier are sites on myelinated axons where the insulating layers of myelin are interrupted. They represent an excellent example of a complex cellular structure that contains highly differentiated sub-regions. At these sites of cell-cell specialization, ion fluxes occur which are required for propagation of action potentials. Myelinated axons and their nodes of Ranvier represent an important evolutionary advance for vertebrates that permit very rapid propagation of action potentials without large increases in axonal diameter. This physiological achievement is based on adaptations at a molecular level resulting in an elegant cooperation between glial cells and the axons of neurons.The organization and sub-specialization of the molecular components of the node of Ranvier are complex but often inter-related. The nodal region of axons are enriched in several channel and pump proteins including the voltage-gated Na+ channel, Na+-K+ ATPase and a number of different K+ channel isotypes.

scholarly journals Alternative Splicing of a Protein Domain Indispensable for Function of Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channels

2012 ◽  
Vol 287 (44) ◽  
pp. 36663-36672 ◽  
Author(s):  
Julia Frühwald ◽  
Julia Camacho Londoño ◽  
Sandeep Dembla ◽  
Stefanie Mannebach ◽  
Annette Lis ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Protein Domain ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

Basis for tetrodotoxin and lidocaine effects on action potentials in dog ventricular myocytes

1988 ◽  
Vol 254 (6) ◽  
pp. H1157-H1166 ◽  
Author(s):  
J. A. Wasserstrom ◽  
J. J. Salata
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Ionic Currents ◽  
Detectable Effect ◽  
Na Channel ◽  
Na Current ◽  
Voltage Range ◽  
Purkinje Fibers ◽  
Ventricular Cells

We studied the effects of tetrodotoxin (TTX) and lidocaine on transmembrane action potentials and ionic currents in dog isolated ventricular myocytes. TTX (0.1-1 x 10(-5) M) and lidocaine (0.5-2 x 10(-5) M) decreased action potential duration, but only TTX decreased the maximum rate of depolarization (Vmax). Both TTX (1-2 x 10(-5) M) and lidocaine (2-5 x 10(-5) M) blocked a slowly inactivating toward current in the plateau voltage range. The voltage- and time-dependent characteristics of this current are virtually identical to those described in Purkinje fibers for the slowly inactivating inward Na+ current. In addition, TTX abolished the outward shift in net current at plateau potentials caused by lidocaine alone. Lidocaine had no detectable effect on the slow inward Ca2+ current and the inward K+ current rectifier, Ia. Our results indicate that 1) there is a slowly inactivating inward Na+ current in ventricular cells similar in time, voltage, and TTX sensitivity to that described in Purkinje fibers; 2) both TTX and lidocaine shorten ventricular action potentials by reducing this slowly inactivating Na+ current; 3) lidocaine has no additional actions on other ionic currents that contribute to its ability to abbreviate ventricular action potentials; and 4) although both agents shorten the action potential by the same mechanism, only TTX reduces Vmax. This last point suggests that TTX produces tonic block of Na+ current, whereas lidocaine may produce state-dependent Na+ channel block, namely, blockade of Na+ current only after Na+ channels have already been opened (inactivated-state block).

scholarly journals Calnexin revealed as an ether-a-go-go chaperone by getting mutant worms up and going

2018 ◽  
Vol 150 (8) ◽  
pp. 1059-1061
Author(s):  
Jonathan T. Pierce
Keyword(s):  
Ion Channels ◽  
Dynamic Control ◽  
Cell Types ◽  
K Channel ◽  
Membrane Domains ◽  
Excitable Cells ◽  
Patch Clamp Recording ◽  
Cell Excitability ◽  
Distinct Membrane

The role of ion channels in cell excitability was first revealed in a series of voltage clamp experiments by Hodgkin and Huxley in the 1950s. However, it was not until the 1970s that patch-clamp recording ushered in a revolution that allowed physiologists to witness how ion channels flicker open and closed at angstrom scale and with microsecond resolution. The unexpectedly tight seal made by the patch pipette in the whole-cell configuration later allowed molecular biologists to suck up the insides of identified cells to unveil their unique molecular contents. By refining these techniques, researchers have scrutinized the surface and contents of excitable cells in detail over the past few decades. However, these powerful approaches do not discern which molecules are responsible for the dynamic control of the genesis, abundance, and subcellular localization of ion channels. In this dark territory, teams of unknown and poorly understood molecules guide specific ion channels through translation, folding, and modification, and then they shuttle them toward and away from distinct membrane domains via different subcellular routes. A central challenge in understanding these processes is the likelihood that these diverse regulatory molecules may be specific to ion channel subtypes, cell types, and circumstance. In work described in this issue, Bai et al. (2018. J. Gen. Physiol. https://doi.org/10.1085/jgp.201812025) begin to shed light on the biogenesis of UNC-103, a K+ channel found in Caenorhabditis elegans.

scholarly journals The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na+channel (ENaC): IUPHAR Review 19

2016 ◽  
Vol 173 (18) ◽  
pp. 2671-2701 ◽  
Author(s):  
Emilie Boscardin ◽  
Omar Alijevic ◽  
Edith Hummler ◽  
Simona Frateschi ◽  
Stephan Kellenberger
Keyword(s):  
Ion Channels ◽  
Na Channel ◽  
Acid Sensing Ion Channels ◽  
Epithelial Na Channel

Hodgkin–Huxley neurons with defective and blocked ion channels

2015 ◽  
Vol 26 (10) ◽  
pp. 1550112 ◽  
Author(s):  
James Christopher S. Pang ◽  
Johnrob Y. Bantang
Keyword(s):  
Ion Channels ◽  
Action Potentials ◽  
Reversal Potential ◽  
Membrane Conductance ◽  
Potassium Ions ◽  
Temporal Response ◽  
Constant Input ◽  
Control Drug ◽  
Channel Control ◽  
Sodium And Potassium

We utilize the original Hodgkin–Huxley (HH) model to consider the effects of defective ion channels to the temporal response of neurons. Statistics of firing rate and inter-spike interval (ISI) reveal that production of action potentials (APs) in neurons is not sensitive to changes in membrane conductance for sodium and potassium ions, as well as to the reversal potential for sodium ions, as long as the relevant parameters do not exceed 13% from their normal levels. We also found that blockage of a critical fraction of either sodium or potassium channels (dependent on constant input current) respectively limits the firing activity or increases spontaneous spiking activity of neurons. Our model may be used to guide experiment designs related to ion channel control drug development.

Abstract 17319: Distinct Effects of Human Calmodulinopathy on the Function of Small Conductance Ca 2+ -Activated K + (SK) Channels

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Hannah A Ledford ◽  
Seojin Park ◽  
Duncan Muir ◽  
Wen Smith ◽  
Ryan L Woltz ◽  
...  
Keyword(s):  
Ion Channels ◽  
Intracellular Signaling ◽  
Critical Role ◽  
Dominant Negative ◽  
Polymorphic Ventricular Tachycardia ◽  
Dominant Negative Effect ◽  
Sk Channels ◽  
Channel Function ◽  
Sk Channel ◽  
Small Conductance

Background: Calmodulin (CaM) plays a critical role in intracellular signaling and regulation of Ca 2+ -dependent ion channels. Mutations in CALM1, CALM2, and CALM3 have recently been linked to cardiac arrhythmias, such as Long QT Syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and familial idiopathic ventricular fibrillation (IVF). Small-conductance Ca 2+ - activated K + channels (SK) are voltage-independent channels that are regulated solely from beat-to-beat changes in intracellular calcium. CaM regulates the function of multiple ion channels, including SK channels, although the effect of CaM mutations on these channels is not yet understood. We hypothesize that human CaM mutations linked to sudden cardiac death disrupt SK channel function by distinct mechanisms. Methods and Results: We tested the effects of LQTS (CaM D96V , CaM D130G ), CPVT (CaM N54I , CaM N98S ), and IVF (CaM F90L ) CaM mutants compared to CaM WT on SK channel function. Using whole-cell voltage-clamp recordings, we found that CaM D96V and CaM D130G mutants significantly inhibited apamin-sensitive currents. Similarly, action potential studies in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) also revealed significant knockdown of apamin-sensitive currents. Immunofluorescent confocal microscopy confirmed that this effect was not due to changes in SK channel trafficking. Rather, co-immunoprecipitation studies showed a significant decrease in the association of these CaM mutants with the SK channel. Rosetta molecular modeling was used to identify a conformational change in CaM F90L structure compared to that of CaM WT . Conclusions: We found that CaM D96V and CaM D130G mutants significantly reduced apamin-sensitive currents, through a dominant negative effect on SK channel function. Consistent with our hypothesis, CaM F90L resulted in the least inhibitory effects. The data suggests that specific mutations with phenylalanine to leucine (CaM F90L ) may disrupt the interaction between apo-CaM with CaMBD on the SK2 channel.

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