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Neuroscience
2014 May 30;268:297-308. doi: 10.1016/j.neuroscience.2014.03.028.
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Sequence variations at I260 and A1731 contribute to persistent currents in Drosophila sodium channels.
Gao R
,
Du Y
,
Wang L
,
Nomura Y
,
Satar G
,
Gordon D
,
Gurevitz M
,
Goldin AL
,
Dong K
.
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Tetrodotoxin-sensitive persistent sodium currents, INaP, that activate at subthreshold voltages, have been detected in numerous vertebrate and invertebrate neurons. These currents are believed to be critical for regulating neuronal excitability. However, the molecular mechanism underlying INaP is controversial. In this study, we identified an INaP with a broad range of voltage dependence, from -60mV to 20mV, in a Drosophila sodium channel variant expressed in Xenopus oocytes. Mutational analysis revealed that two variant-specific amino acid changes, I260T in the S4-S5 linker of domain I (ILS4-S5) and A1731V in the voltage sensor S4 of domain IV (IVS4), contribute to the INaP. I260T is critical for the portion of INaP at hyperpolarized potentials. The T260-mediated INaP is likely the result of window currents flowing in the voltage range where the activation and inactivation curves overlap. A1731V is responsible for impaired inactivation and contributes to the portion of INaP at depolarized potentials. Furthermore, A1731V causes enhanced activity of two site-3 toxins which induce persistent currents by inhibiting the outward movement of IVS4, suggesting that A1731V inhibits the outward movement of IVS4. These results provided molecular evidence for the involvement of distinct mechanisms in the generation of INaP: T260 contributes to INaP via enhancement of the window current, whereas V1731 impairs fast inactivation probably by inhibiting the outward movement of IVS4.
Ahn,
A new Nav1.7 sodium channel mutation I234T in a child with severe pain.
2010, Pubmed
Ahn,
A new Nav1.7 sodium channel mutation I234T in a child with severe pain.
2010,
Pubmed
Campos,
Effects of bound ts3 on voltage dependence of sodium channel transitions to and from inactivation and energetics of its unbinding.
2006,
Pubmed
Catterall,
Voltage-gated sodium channels at 60: structure, function and pathophysiology.
2012,
Pubmed
Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed
Chahine,
Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation.
1994,
Pubmed
Chanda,
Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation.
2002,
Pubmed
,
Xenbase
Chatelier,
Biophysical characterisation of the persistent sodium current of the Nav1.6 neuronal sodium channel: a single-channel analysis.
2010,
Pubmed
Chen,
Modulation of cloned skeletal muscle sodium channels by the scorpion toxins Lqh II, Lqh III, and Lqh alphaIT.
2000,
Pubmed
Chen,
Transient and persistent tetrodotoxin-sensitive sodium currents in squid olfactory receptor neurons.
1999,
Pubmed
Chen,
A unique role for the S4 segment of domain 4 in the inactivation of sodium channels.
1996,
Pubmed
,
Xenbase
Clay,
On the persistent sodium current in squid giant axons.
2003,
Pubmed
Crill,
Persistent sodium current in mammalian central neurons.
1996,
Pubmed
Dib-Hajj,
NaN/Nav1.9: a sodium channel with unique properties.
2002,
Pubmed
Dong,
Insect sodium channels and insecticide resistance.
2007,
Pubmed
,
Xenbase
Feng,
Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function.
1995,
Pubmed
,
Xenbase
Goldin,
Nomenclature of voltage-gated sodium channels.
2000,
Pubmed
Goldschen-Ohm,
Multiple pore conformations driven by asynchronous movements of voltage sensors in a eukaryotic sodium channel.
2013,
Pubmed
,
Xenbase
Gur,
Elucidation of the molecular basis of selective recognition uncovers the interaction site for the core domain of scorpion alpha-toxins on sodium channels.
2011,
Pubmed
,
Xenbase
Hanck,
Site-3 toxins and cardiac sodium channels.
2007,
Pubmed
Jackson,
Mechanism of spontaneous firing in dorsomedial suprachiasmatic nucleus neurons.
2004,
Pubmed
Khaliq,
Pacemaking in dopaminergic ventral tegmental area neurons: depolarizing drive from background and voltage-dependent sodium conductances.
2010,
Pubmed
Kiss,
Persistent Na-channels: origin and function. A review.
2008,
Pubmed
Kiss,
Food-aversive classical conditioning increases a persistent sodium current in molluscan withdrawal interneurons in a transcription dependent manner.
2009,
Pubmed
Kontis,
Sodium channel activation gating is affected by substitutions of voltage sensor positive charges in all four domains.
1997,
Pubmed
,
Xenbase
Kühn,
Movement of voltage sensor S4 in domain 4 is tightly coupled to sodium channel fast inactivation and gating charge immobilization.
1999,
Pubmed
,
Xenbase
Lampert,
Upregulation of persistent and ramp sodium current in dorsal horn neurons after spinal cord injury.
2006,
Pubmed
Lampert,
Size matters: Erythromelalgia mutation S241T in Nav1.7 alters channel gating.
2006,
Pubmed
Lapied,
Sensitive nicotinic and mixed nicotinic-muscarinic receptors in insect neurosecretory cells.
1990,
Pubmed
Lin,
Alternative splicing in the voltage-gated sodium channel DmNav regulates activation, inactivation, and persistent current.
2009,
Pubmed
,
Xenbase
Lin,
Activity-dependent alternative splicing increases persistent sodium current and promotes seizure.
2012,
Pubmed
Liu,
Persistent tetrodotoxin-sensitive sodium current resulting from U-to-C RNA editing of an insect sodium channel.
2004,
Pubmed
Llinás,
Electrophysiology of the mammillary complex in vitro. I. Tuberomammillary and lateral mammillary neurons.
1992,
Pubmed
Loughney,
Molecular analysis of the para locus, a sodium channel gene in Drosophila.
1989,
Pubmed
Magistretti,
Direct demonstration of persistent Na+ channel activity in dendritic processes of mammalian cortical neurones.
1999,
Pubmed
Magistretti,
High conductance sustained single-channel activity responsible for the low-threshold persistent Na(+) current in entorhinal cortex neurons.
1999,
Pubmed
Mee,
Regulation of neuronal excitability through pumilio-dependent control of a sodium channel gene.
2004,
Pubmed
Moran,
Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels.
2007,
Pubmed
,
Xenbase
Olson,
Molecular and functional characterization of voltage-gated sodium channel variants from Drosophila melanogaster.
2008,
Pubmed
,
Xenbase
Opdyke,
A persistent sodium current contributes to oscillatory activity in heart interneurons of the medicinal leech.
1994,
Pubmed
Park,
Identification of alternative splicing regulators by RNA interference in Drosophila.
2004,
Pubmed
Pennartz,
Cellular mechanisms underlying spontaneous firing in rat suprachiasmatic nucleus: involvement of a slowly inactivating component of sodium current.
1997,
Pubmed
Rakowski,
Single ion occupancy and steady-state gating of Na channels in squid giant axon.
2002,
Pubmed
Raman,
Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei.
2000,
Pubmed
Rogers,
Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit.
1996,
Pubmed
Sheets,
The Na channel voltage sensor associated with inactivation is localized to the external charged residues of domain IV, S4.
1999,
Pubmed
Sheets,
Gating of skeletal and cardiac muscle sodium channels in mammalian cells.
1999,
Pubmed
Sheets,
Voltage-dependent open-state inactivation of cardiac sodium channels: gating current studies with Anthopleurin-A toxin.
1995,
Pubmed
Sheets,
Charge immobilization of the voltage sensor in domain IV is independent of sodium current inactivation.
2005,
Pubmed
Sheets,
Outward stabilization of the S4 segments in domains III and IV enhances lidocaine block of sodium channels.
2007,
Pubmed
Smith,
Functional analysis of the mouse Scn8a sodium channel.
1998,
Pubmed
,
Xenbase
Stafstrom,
Persistent sodium current and its role in epilepsy.
2007,
Pubmed
Sun,
Carbamazepine and topiramate modulation of transient and persistent sodium currents studied in HEK293 cells expressing the Na(v)1.3 alpha-subunit.
2007,
Pubmed
Taddese,
Subthreshold sodium current from rapidly inactivating sodium channels drives spontaneous firing of tuberomammillary neurons.
2002,
Pubmed
Tan,
Identification of amino acid residues in the insect sodium channel critical for pyrethroid binding.
2005,
Pubmed
,
Xenbase
Taylor,
Na+ currents that fail to inactivate.
1993,
Pubmed
Tejedor,
Site of covalent attachment of alpha-scorpion toxin derivatives in domain I of the sodium channel alpha subunit.
1988,
Pubmed
Thomsen,
Localization of the receptor site for alpha-scorpion toxins by antibody mapping: implications for sodium channel topology.
1989,
Pubmed
Uteshev,
A persistent sodium current in acutely isolated histaminergic neurons from rat hypothalamus.
1995,
Pubmed
Wang,
Mapping the receptor site for alpha-scorpion toxins on a Na+ channel voltage sensor.
2011,
Pubmed
Warmke,
Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology.
1997,
Pubmed
,
Xenbase
Yamada-Hanff,
Persistent sodium current drives conditional pacemaking in CA1 pyramidal neurons under muscarinic stimulation.
2013,
Pubmed
Yang,
The position of the fourth segment of domain 4 determines status of the inactivation gate in Na+ channels.
2003,
Pubmed
,
Xenbase
Yu,
Overview of the voltage-gated sodium channel family.
2003,
Pubmed
Zilberberg,
Functional expression and genetic alteration of an alpha scorpion neurotoxin.
1996,
Pubmed
