Integration and recording of a reconstituted voltage-gated sodium channel in planar lipid bilayers

2011 ◽  
Vol 26 (5) ◽  
pp. 1924-1928 ◽  
Author(s):  
A. Studer ◽  
S. Demarche ◽  
D. Langenegger ◽  
L. Tiefenauer
Keyword(s):  
Sodium Channel ◽  
Lipid Bilayers ◽  
Planar Lipid Bilayers ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

scholarly journals Manipulation of a spider peptide toxin alters its affinity for lipid bilayers and potency and selectivity for voltage-gated sodium channel subtype 1.7

2020 ◽  
Vol 295 (15) ◽  
pp. 5067-5080 ◽  
Author(s):  
Akello J. Agwa ◽  
Poanna Tran ◽  
Alexander Mueller ◽  
Hue N. T. Tran ◽  
Jennifer R. Deuis ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Lipid Membrane ◽  
Surface Profile ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Gating Modifier ◽  
Peptide Toxin

Huwentoxin-IV (HwTx-IV) is a gating modifier peptide toxin from spiders that has weak affinity for the lipid bilayer. As some gating modifier toxins have affinity for model lipid bilayers, a tripartite relationship among gating modifier toxins, voltage-gated ion channels, and the lipid membrane surrounding the channels has been proposed. We previously designed an HwTx-IV analogue (gHwTx-IV) with reduced negative charge and increased hydrophobic surface profile, which displays increased lipid bilayer affinity and in vitro activity at the voltage-gated sodium channel subtype 1.7 (NaV1.7), a channel targeted in pain management. Here, we show that replacements of the positively-charged residues that contribute to the activity of the peptide can improve gHwTx-IV's potency and selectivity for NaV1.7. Using HwTx-IV, gHwTx-IV, [R26A]gHwTx-IV, [K27A]gHwTx-IV, and [R29A]gHwTx-IV variants, we examined their potency and selectivity at human NaV1.7 and their affinity for the lipid bilayer. [R26A]gHwTx-IV consistently displayed the most improved potency and selectivity for NaV1.7, examined alongside off-target NaVs, compared with HwTx-IV and gHwTx-IV. The lipid affinity of each of the three novel analogues was weaker than that of gHwTx-IV, but stronger than that of HwTx-IV, suggesting a possible relationship between in vitro potency at NaV1.7 and affinity for lipid bilayers. In a murine NaV1.7 engagement model, [R26A]gHwTx-IV exhibited an efficacy comparable with that of native HwTx-IV. In summary, this study reports the development of an HwTx-IV analogue with improved in vitro selectivity for the pain target NaV1.7 and with an in vivo efficacy similar to that of native HwTx-IV.

The Voltage-Gated Sodium Channel Nav1.2 Contributes to Neurodegeneration in an Animal Model of Multiple Sclerosis

2016 ◽  
Vol 47 (S 01) ◽  
Author(s):  
W. Fazeli ◽  
B. Schattling ◽  
B. Engeland ◽  
M. Friese ◽  
D. Isbrand
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

Homozygous SCN1B variants causing early infantile epileptic encephalopathy 52 affect voltage‐gated sodium channel function

Epilepsia ◽  
2021 ◽  
Author(s):  
Marcello Scala ◽  
Stephanie Efthymiou ◽  
Tipu Sultan ◽  
Jolien De Waele ◽  
Marta Panciroli ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Epileptic Encephalopathy ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Function

Neonatal Na V 1.5: Pharmacological distinctiveness of a cancer‐related voltage‐gated sodium channel splice variant

2021 ◽  
Author(s):  
Scott P. Fraser ◽  
Rustem Onkal ◽  
Margaux Theys ◽  
Frank Bosmans ◽  
Mustafa B. A. Djamgoz
Keyword(s):  
Sodium Channel ◽  
Splice Variant ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated
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