The outermost lysine in the S4 of domain III contributes little to the gating charge in sodium channels.

  title={The outermost lysine in the S4 of domain III contributes little to the gating charge in sodium channels.},
  author={Michael F. Sheets and Dorothy A. Hanck},
  journal={Biophysical journal},
  volume={82 6},
Role of Domain IV/S4 outermost arginines in gating of T-type calcium channels
Together, the data indicate that Domain IV/S4 is an activation domain and is not involved in inactivation from the open state.
Outward stabilization of the S4 segments in domains III and IV enhances lidocaine block of sodium channels
It is concluded that the positions of the S4s in domains III and IV are major determinants of the voltage dependence of lidocaine affinity.
Central Charged Residues in DIIIS4 Regulate Deactivation Gating in Skeletal Muscle Sodium Channels
Summary1. Mutations in the S4 segment of domain III in the voltage gated skeletal muscle sodium channel hNaV1.4 were constructed to test the roles of each charged residue in deactivation gating.
Outward stabilization of the voltage sensor in domain II but not domain I speeds inactivation of voltage-gated sodium channels.
The leftward shifts of both activation and inactivation and the decrease in Gmax after stabilization of the DII-S4 support previous studies that showed β-scorpion toxins trap the voltage sensor of DII in an activated conformation.
Molecular Action of Lidocaine on the Voltage Sensors of Sodium Channels
Lidocaine's most dramatic effect was to alter the voltage-dependent charge movement of the S4 in domain IV such that it accounted for the appearance of additional gating charge at potentials near −100 mV, suggesting that lidOCaine's actions on Na channel gatingcharge result from allosteric coupling of the binding site(s) of lidocaine to the voltage sensors formed by the S 4 segments in domains III and IV.
The Unique Role of the Domain IV Voltage-Sensor in Sodium Channel Inactivation and Gating
This study characterizes the role of individual voltage-sensors in the processes of both fast and slow inactivation and identifies domain IV S4 as the crucial Voltage-sensor involved in fast inactivation.
Structure and function of potassium and calcium channels.
Investigation of residue 263 indicated that this movement occurs at potentials more negative than the resting membrane potential of -80mV, which suggests that under depolarising conditions the S4 segment is exposed to the extracellular environment up to and including residue 268, with residues 269 and 271 remaining buried.
Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis.
The voltage sensor module in sodium channels.
  • J. Groome
  • Biology
    Handbook of experimental pharmacology
  • 2014
Crystallography, structural and homology modeling, and molecular dynamics simulations have added computational approaches to study the relationship of channel structure to function to define the present understanding of the mechanism by which the voltage sensor module dictates gating particle permissiveness in excitable cells.
Molecular regions underlying the activation of low- and high-voltage activating calcium channels
During channel activation, the reagent parachloromercuribenzensulfonate inhibited currents for mutants V263, A265, L266 and A268, but not for F269 and V271, and voltage dependence of inhibition for residue V263 indicated S4 movement, which occurred before channel opening.


A unique role for the S4 segment of domain 4 in the inactivation of sodium channels
The voltage dependence of inactivation time constants is markedly decreased by mutations only in S4D4, providing further evidence that this segment plays a unique role in activation-inactivation coupling.
Movement of Voltage Sensor S4 in Domain 4 Is Tightly Coupled to Sodium Channel Fast Inactivation and Gating Charge Immobilization
It is demonstrated that S4D4 is one of the immobilized voltage sensors during the manifestation of the inactivated state, and an intimate coupling of these two processes that is maintained in the mutations is demonstrated.
A Specific Interaction between the Cardiac Sodium Channel and Site-3 Toxin Anthopleurin B*
The polypeptide neurotoxin anthopleurin B (ApB) isolated from the venom of the sea anemone Anthopleura xanthogrammica is one of a family of toxins that bind to the extracellular face of
Multiple cationic residues of anthopleurin B that determine high affinity and channel isoform discrimination.
The role of cationic residues is investigated by characterizing toxin mutants in which two such residues are replaced simultaneously, which reduced affinity of the toxin for neuronal channels to a much greater extent than for cardiac channels and produced affinities only slightly lower than for ApA in each case.
Sodium Channel Activation Gating Is Affected by Substitutions of Voltage Sensor Positive Charges in All Four Domains
The data support the idea that both charge and structure are determinants of function in S4 voltage sensors, and a working model in which all four S4 segments contribute to voltage-dependent activation of the sodium channel.
The Role of the Putative Inactivation Lid in Sodium Channel Gating Current Immobilization
It is concluded that movement of domain IV-S4 is the rate-limiting step during repolarization, and it contributes to charge immobilization regardless of whether the inactivation lid is bound, and likewise for ICM-hH1aMTSET in control.
Site of covalent attachment of alpha-scorpion toxin derivatives in domain I of the sodium channel alpha subunit.
  • F. Tejedor, W. Catterall
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1988
It is proposed that a portion of the receptor site for alpha-scorpion toxins is formed by peptide segment(s) between amino acid residues 335 and 378 which is located in an extracellular loop between transmembrane helices S5 and S6 of homologous domain I of the sodium channel alpha subunit.