scholarly journals Structure and Function of the Voltage Sensor of Sodium Channels Probed by a β-Scorpion Toxin

2006 ◽  
Vol 281 (30) ◽  
pp. 21332-21344 ◽  
Author(s):  
Sandrine Cestèle ◽  
Vladimir Yarov-Yarovoy ◽  
Yusheng Qu ◽  
François Sampieri ◽  
Todd Scheuer ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Structure And Function ◽  
Voltage Sensor ◽  
Scorpion Toxin ◽  
And Function

Chapter 17 Voltage-Sensitive Sodium Channels: Molecular Structure and Function

1988 ◽  
pp. 329-365 ◽  
Author(s):  
William S. Agnew ◽  
Edward C. Cooper ◽  
William M. James ◽  
Sally A. Tomiko ◽  
Robert L. Rosenberg ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Sodium Channels ◽  
Structure And Function ◽  
And Function ◽  
Molecular Structure And Function

Structure and Function of Sodium Channels

1993 ◽  
Vol 3 (5-6) ◽  
pp. 277-282 ◽  
Author(s):  
Walter Stühmer
Keyword(s):  
Sodium Channels ◽  
Structure And Function ◽  
And Function

scholarly journals Structure and function of the β2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif

Cell ◽  
1995 ◽  
Vol 83 (3) ◽  
pp. 433-442 ◽  
Author(s):  
L.L. Isom ◽  
D.S. Ragsdale ◽  
K.S. De Jongh ◽  
R.E. Westenbroek ◽  
B.F.X. Reber ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Structure And Function ◽  
Transmembrane Glycoprotein ◽  
And Function

scholarly journals Structure and function of voltage-gated sodium channels

1998 ◽  
Vol 508 (3) ◽  
pp. 647-657 ◽  
Author(s):  
Eduardo Marban ◽  
Toshio Yamagishi ◽  
Gordon F. Tomaselli
Keyword(s):  
Sodium Channels ◽  
Structure And Function ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
And Function

scholarly journals Simplified Bacterial “Pore” Channel Provides Insight into the Assembly, Stability, and Structure of Sodium Channels

2011 ◽  
Vol 286 (18) ◽  
pp. 16386-16391 ◽  
Author(s):  
Emily C. McCusker ◽  
Nazzareno D'Avanzo ◽  
Colin G. Nichols ◽  
B. A. Wallace
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Structural Features ◽  
Voltage Sensor ◽  
Full Length ◽  
Pore Channel ◽  
Folded Structure ◽  
High Level ◽  
And Function ◽  
Electrical Signaling

Eukaryotic sodium channels are important membrane proteins involved in ion permeation, homeostasis, and electrical signaling. They are long, multidomain proteins that do not express well in heterologous systems, and hence, structure/function and biochemical studies on purified sodium channel proteins have been limited. Bacteria produce smaller, homologous tetrameric single domain channels specific for the conductance of sodium ions. They consist of N-terminal voltage sensor and C-terminal pore subdomains. We designed a functional pore-only channel consisting of the final two transmembrane helices, the intervening P-region, and the C-terminal extramembranous region of the sodium channel from the marine bacterium Silicibacter pomeroyi. This sodium “pore” channel forms a tetrameric, folded structure that is capable of supporting sodium flux in phospholipid vesicles. The pore-only channel is more thermally stable than its full-length counterpart, suggesting that the voltage sensor subdomain may destabilize the full-length channel. The pore subdomains can assemble, fold, and function independently from the voltage sensor and exhibit similar ligand-blocking characteristics as the intact channel. The availability of this simple pore-only construct should enable high-level expression for the testing of potential new ligands and enhance our understanding of the structural features that govern sodium selectivity and permeability.

scholarly journals Neutralization of Gating Charges in Domain II of the Sodium Channel α Subunit Enhances Voltage-Sensor Trapping by a β-Scorpion Toxin

2001 ◽  
Vol 118 (3) ◽  
pp. 291-302 ◽  
Author(s):  
Sandrine Cestèle ◽  
Todd Scheuer ◽  
Massimo Mantegazza ◽  
Hervé Rochat ◽  
William A. Catterall
Keyword(s):  
Sodium Channel ◽  
Sodium Channels ◽  
Voltage Dependence ◽  
Membrane Potentials ◽  
Voltage Sensor ◽  
Scorpion Toxin ◽  
Channel Activation ◽  
Α Subunit ◽  
Gating Charges

β-Scorpion toxins shift the voltage dependence of activation of sodium channels to more negative membrane potentials, but only after a strong depolarizing prepulse to fully activate the channels. Their receptor site includes the S3–S4 loop at the extracellular end of the S4 voltage sensor in domain II of the α subunit. Here, we probe the role of gating charges in the IIS4 segment in β-scorpion toxin action by mutagenesis and functional analysis of the resulting mutant sodium channels. Neutralization of the positively charged amino acid residues in the IIS4 segment by mutation to glutamine shifts the voltage dependence of channel activation to more positive membrane potentials and reduces the steepness of voltage-dependent gating, which is consistent with the presumed role of these residues as gating charges. Surprisingly, neutralization of the gating charges at the outer end of the IIS4 segment by the mutations R850Q, R850C, R853Q, and R853C markedly enhances β-scorpion toxin action, whereas mutations R856Q, K859Q, and K862Q have no effect. In contrast to wild-type, the β-scorpion toxin Css IV causes a negative shift of the voltage dependence of activation of mutants R853Q and R853C without a depolarizing prepulse at holding potentials from −80 to −140 mV. Reaction of mutant R853C with 2-aminoethyl methanethiosulfonate causes a positive shift of the voltage dependence of activation and restores the requirement for a depolarizing prepulse for Css IV action. Enhancement of sodium channel activation by Css IV causes large tail currents upon repolarization, indicating slowed deactivation of the IIS4 voltage sensor by the bound toxin. Our results are consistent with a voltage-sensor–trapping model in which the β-scorpion toxin traps the IIS4 voltage sensor in its activated position as it moves outward in response to depolarization and holds it there, slowing its inward movement on deactivation and enhancing subsequent channel activation. Evidently, neutralization of R850 and R853 removes kinetic barriers to binding of the IIS4 segment by Css IV, and thereby enhances toxin-induced channel activation.

Effects of Deglycosylation of Sodium Channels on Their Structure and Function†

Biochemistry ◽  
2005 ◽  
Vol 44 (2) ◽  
pp. 441-449 ◽  
Author(s):  
Nora B. Cronin ◽  
Andrias O'Reilly ◽  
Hervé Duclohier ◽  
B. A. Wallace
Keyword(s):  
Sodium Channels ◽  
Structure And Function ◽  
And Function
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