scholarly journals The neurosteroid allopregnanolone sulfate inhibits Nav1.3 α subunit-containing voltage-gated sodium channels, expressed in Xenopus oocytes

2018 ◽  
Vol 137 (1) ◽  
pp. 93-97 ◽  
Author(s):  
Takafumi Horishita ◽  
Nobuyuki Yanagihara ◽  
Susumu Ueno ◽  
Dan Okura ◽  
Reiko Horishita ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Xenopus Oocytes ◽  
Α Subunit ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Neurosteroids Allopregnanolone Sulfate and Pregnanolone Sulfate Have Diverse Effect on the α Subunit of the Neuronal Voltage-gated Sodium Channels Nav1.2, Nav1.6, Nav1.7, and Nav1.8 Expressed in Xenopus Oocytes

2014 ◽  
Vol 121 (3) ◽  
pp. 620-631 ◽  
Author(s):  
Takafumi Horishita ◽  
Nobuyuki Yanagihara ◽  
Susumu Ueno ◽  
Yuka Sudo ◽  
Yasuhito Uezono ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Xenopus Oocytes ◽  
Sodium Current ◽  
Dependent Manner ◽  
Sodium Currents ◽  
Concentration Dependent Manner ◽  
Α Subunit ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Α Subunits

Abstract Background: The neurosteroids allopregnanolone and pregnanolone are potent positive modulators of γ-aminobutyric acid type A receptors. Antinociceptive effects of allopregnanolone have attracted much attention because recent reports have indicated the potential of allopregnanolone as a therapeutic agent for refractory pain. However, the analgesic mechanisms of allopregnanolone are still unclear. Voltage-gated sodium channels (Nav) are thought to play important roles in inflammatory and neuropathic pain, but there have been few investigations on the effects of allopregnanolone on sodium channels. Methods: Using voltage-clamp techniques, the effects of allopregnanolone sulfate (APAS) and pregnanolone sulfate (PAS) on sodium current were examined in Xenopus oocytes expressing Nav1.2, Nav1.6, Nav1.7, and Nav1.8 α subunits. Results: APAS suppressed sodium currents of Nav1.2, Nav1.6, and Nav1.7 at a holding potential causing half-maximal current in a concentration-dependent manner, whereas it markedly enhanced sodium current of Nav1.8 at a holding potential causing maximal current. Half-maximal inhibitory concentration values for Nav1.2, Nav1.6, and Nav1.7 were 12 ± 4 (n = 6), 41 ± 2 (n = 7), and 131 ± 15 (n = 5) μmol/l (mean ± SEM), respectively. The effects of PAS were lower than those of APAS. From gating analysis, two compounds increased inactivation of all α subunits, while they showed different actions on activation of each α subunit. Moreover, two compounds showed a use-dependent block on Nav1.2, Nav1.6, and Nav1.7. Conclusion: APAS and PAS have diverse effects on sodium currents in oocytes expressing four α subunits. APAS inhibited the sodium currents of Nav1.2 most strongly.

scholarly journals Carvacrol inhibits the neuronal voltage-gated sodium channels Nav1.2, Nav1.6, Nav1.3, Nav1.7, and Nav1.8 expressed in Xenopus oocytes with different potencies

2020 ◽  
Vol 142 (4) ◽  
pp. 140-147
Author(s):  
Takafumi Horishita ◽  
Yuichi Ogata ◽  
Reiko Horishita ◽  
Ryo Fukui ◽  
Kuniaki Moriwaki ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Xenopus Oocytes ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

The Endocannabinoid Anandamide Inhibits Voltage-Gated Sodium Channels Nav1.2, Nav1.6, Nav1.7, and Nav1.8 in Xenopus Oocytes

2014 ◽  
Vol 118 (3) ◽  
pp. 554-562 ◽  
Author(s):  
Dan Okura ◽  
Takafumi Horishita ◽  
Susumu Ueno ◽  
Nobuyuki Yanagihara ◽  
Yuka Sudo ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Xenopus Oocytes ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Nav1.5 cardiac sodium channels, regulation and clinical implications

2015 ◽  
Vol 62 (4) ◽  
pp. 587-592
Author(s):  
Henry Humberto León Ariza ◽  
Natalia Valenzuela Faccini ◽  
Ariana Carolina Rojas Ortega ◽  
Daniel Alfonso Botero Rosas
Keyword(s):  
Sodium Channels ◽  
Calcium Concentration ◽  
Extracellular Proteins ◽  
The Body ◽  
Clinical Implications ◽  
Α Subunit ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Qt Syndrome ◽  
Cardiac Sodium Channels

<p>Voltage-gated sodium channels constitute a group of membrane<br />proteins widely distributed thought the body. In the heart, there<br />are at least six different isoforms, being the Nav1.5 the most<br />abundant. The channel is composed of an α subunit that is formed<br />by four domains of six segments each, and four much smaller β<br />subunits that provide stability and integrate other channels into<br />the α subunit. The function of the Nav1.5 channel is modulated<br />by intracellular cytoskeleton proteins, extracellular proteins,<br />calcium concentration, free radicals, and medications, among<br />other things. The study of the channel and its alterations has<br />grown thanks to its association with pathogenic conditions such<br />as Long QT syndrome, Brugada syndrome, atrial fibrillation,<br />arrhythmogenic ventricular dysplasia and complications during<br />ischemic processes.</p>

scholarly journals Molecular Determinants of Brevetoxin Binding to Voltage-Gated Sodium Channels

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 513 ◽  
Author(s):  
Keiichi Konoki ◽  
Daniel G. Baden ◽  
Todd Scheuer ◽  
William A. Catterall
Keyword(s):  
Sodium Channels ◽  
Red Tides ◽  
Shellfish Poisoning ◽  
Alanine Scanning Mutagenesis ◽  
Α Subunit ◽  
Voltage Gated ◽  
Transmembrane Segments ◽  
Voltage Gated Sodium Channels ◽  
Fold Reduction ◽  
Molecular Determinants

Brevetoxins are produced by dinoflagellates such as Karenia brevis in warm-water red tides and cause neurotoxic shellfish poisoning. They bind to voltage-gated sodium channels at neurotoxin receptor 5, making the channels more active by shifting the voltage-dependence of activation to more negative potentials and by slowing the inactivation process. Previous work using photoaffinity labeling identified binding to the IS6 and IVS5 transmembrane segments of the channel α subunit. We used alanine-scanning mutagenesis to identify molecular determinants for brevetoxin binding in these regions as well as adjacent regions IVS5-SS1 and IVS6. Most of the mutant channels containing single alanine substitutions expressed functional protein in tsA-201 cells and bound to the radioligand [42-3H]-PbTx3. Binding affinity for the great majority of mutant channels was indistinguishable from wild type. However, transmembrane segments IS6, IVS5 and IVS6 each contained 2 to 4 amino acid positions where alanine substitution resulted in a 2–3-fold reduction in brevetoxin affinity, and additional mutations caused a similar increase in brevetoxin affinity. These findings are consistent with a model in which brevetoxin binds to a protein cleft comprising transmembrane segments IS6, IVS5 and IVS6 and makes multiple distributed interactions with these α helices. Determination of brevetoxin affinity for Nav1.2, Nav1.4 and Nav1.5 channels showed that Nav1.5 channels had a characteristic 5-fold reduction in affinity for brevetoxin relative to the other channel isoforms, suggesting the interaction with sodium channels is specific despite the distributed binding determinants.

scholarly journals Inhibition by Pregnenolone Sulphate, a Metabolite of the Neurosteroid Pregnenolone, of Voltage-Gated Sodium Channels Expressed in Xenopus Oocytes

2012 ◽  
Vol 120 (1) ◽  
pp. 54-58 ◽  
Author(s):  
Takafumi Horishita ◽  
Susumu Ueno ◽  
Nobuyuki Yanagihara ◽  
Yuka Sudo ◽  
Yasuhito Uezono ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Xenopus Oocytes ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Voltage-gated sodium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
William A. Catterall ◽  
Alan L. Goldin ◽  
Stephen G. Waxman
Keyword(s):  
Sodium Channels ◽  
Ion Selectivity ◽  
Structural Features ◽  
Fatty Acyl ◽  
Transmembrane Segment ◽  
Α Subunit ◽  
Voltage Gated ◽  
Transmembrane Segments ◽  
Voltage Gated Sodium Channels ◽  
Acyl Chains

Sodium channels are voltage-gated sodium-selective ion channels present in the membrane of most excitable cells. Sodium channels comprise of one pore-forming α subunit, which may be associated with either one or two β subunits [176]. α-Subunits consist of four homologous domains (I–IV), each containing six transmembrane segments (S1–S6) and a pore-forming loop. The positively charged fourth transmembrane segment (S4) acts as a voltage sensor and is involved in channel gating. The crystal structure of the bacterial NavAb channel has revealed a number of novel structural features compared to earlier potassium channel structures including a short selectivity filter with ion selectivity determined by interactions with glutamate side chains [268]. Interestingly, the pore region is penetrated by fatty acyl chains that extend into the central cavity which may allow the entry of small, hydrophobic pore-blocking drugs [268]. Auxiliary β1, β2, β3 and β4 subunits consist of a large extracellular N-terminal domain, a single transmembrane segment and a shorter cytoplasmic domain.The nomenclature for sodium channels was proposed by Goldin et al., (2000) [143] and approved by the NC-IUPHAR Subcommittee on sodium channels (Catterall et al., 2005, [51]).

scholarly journals Voltage-gated sodium channels (NaV) in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
William A. Catterall ◽  
Alan L. Goldin ◽  
Stephen G. Waxman
Keyword(s):  
Sodium Channels ◽  
Ion Selectivity ◽  
Structural Features ◽  
Fatty Acyl ◽  
Transmembrane Segment ◽  
Α Subunit ◽  
Voltage Gated ◽  
Transmembrane Segments ◽  
Voltage Gated Sodium Channels ◽  
Acyl Chains

Sodium channels are voltage-gated sodium-selective ion channels present in the membrane of most excitable cells. Sodium channels comprise of one pore-forming α subunit, which may be associated with either one or two β subunits [177]. α-Subunits consist of four homologous domains (I-IV), each containing six transmembrane segments (S1-S6) and a pore-forming loop. The positively charged fourth transmembrane segment (S4) acts as a voltage sensor and is involved in channel gating. The crystal structure of the bacterial NavAb channel has revealed a number of novel structural features compared to earlier potassium channel structures including a short selectivity filter with ion selectivity determined by interactions with glutamate side chains [274]. Interestingly, the pore region is penetrated by fatty acyl chains that extend into the central cavity which may allow the entry of small, hydrophobic pore-blocking drugs [274]. Auxiliary β1, β2, β3 and β4 subunits consist of a large extracellular N-terminal domain, a single transmembrane segment and a shorter cytoplasmic domain.The nomenclature for sodium channels was proposed by Goldin et al., (2000) [144] and approved by the NC-IUPHAR Subcommittee on sodium channels (Catterall et al., 2005, [52]).

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