How Does the W434F Mutation Block Current in Shaker Potassium Channels?

The mutation W434F produces an apparently complete block of potassium current in Shaker channels expressed in Xenopus oocytes. Tandem tetrameric constructs containing one or two subunits with this mutation showed rapid inactivation, although the NH2-terminal inactivation domain was absent from these constructs. The inactivation showed a selective dependence on external cations and was slowed by external TEA; these properties are characteristic of C-type inactivation. Inactivation was, however, incompletely relieved by hyperpolarization, suggesting the presence of a voltage-independent component. The hybrid channels had near-normal conductance and ion selectivity. Single-channel recordings from patches containing many W434F channels showed occasional channel openings, consistent with open probabilities of 10−5 or less. We conclude that the W434F mutation produces a channel that is predominantly found in an inactivated state.

• Publication year

  1997

• Venue

  The Journal of General Physiology

• Publication date

  1997-06-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1085/JGP.109.6.779PMID 9222903PMCID 2217041
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Inactivation determined by a single site in K+ pores

  2004cited by this paper
• Slow gating charge immobilization in the human potassium channel Kv1.5 and its prevention by 4‐aminopyridine.

  1996cited by this paper
• Recovery from C-type inactivation is modulated by extracellular potassium.

  1996cited by this paper
• Silver as a probe of pore-forming residues in a potassium channel.

  1995cited by this paper
• C-type inactivation of a voltage-gated K+ channel occurs by a cooperative mechanism.

  1995cited by this paper
• Single-Channel Recording

  1995cited by this paper
• Side-chain accessibilities in the pore of a K+ channel probed by sulfhydryl-specific reagents after cysteine-scanning mutagenesis.

  1995cited by this paper
• Potassium channel assembly from concatenated subunits: effects of proline substitutions in S4 segments.

  1995cited by this paper
• Cooperative subunit interactions in C-type inactivation of K channels.

  1995cited by this paper
• Na+ channels must deactivate to recover from inactivation.

  1994cited by this paper
• Mutations in the K+ channel signature sequence.

  1994cited by this paper
• An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding.

  1994cited by this paper
• Gating current noise produced by elementary transitions in Shaker potassium channels.

  1994cited by this paper
• Gating currents from a nonconducting mutant reveal open-closed conformations in Shaker K+ channels.

  1993cited by this paper
• Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.

  1993influential reference
• A single nonpolar residue in the deep pore of related K+ channels acts as a K+:Rb+ conductance switch.

  1992cited by this paper
• Evidence for cooperative interactions in potassium channel gating

  1992cited by this paper
• Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.

  1992cited by this paper
• Cooperative interactions among subunits of a voltage-dependent potassium channel. Evidence from expression of concatenated cDNAs.

  1992cited by this paper
• Gating currents in Shaker K+ channels. Implications for activation and inactivation models.

  1992cited by this paper
• Extracellular K+ specifically modulates a rat brain K+ channel.

  1992cited by this paper
• The aromatic binding site for tetraethylammonium ion on potassium channels.

  1992cited by this paper
• Tandem linkage of Shaker K+ channel subunits does not ensure the stoichiometry of expressed channels.

  1992cited by this paper
• Alteration of ionic selectivity of a K+ channel by mutation of the H5 region

  1991cited by this paper
• Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region.

  1991cited by this paper
• Molecular basis of gating charge immobilization in Shaker potassium channels.

  1991cited by this paper
• Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels.

  1991cited by this paper
• Biophysical and molecular mechanisms of Shaker potassium channel inactivation

  1990influential reference
• Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain.

  1990cited by this paper
• TEA prevents inactivation while blocking open K+ channels in human T lymphocytes.

  1989cited by this paper
• Multiple potassium-channel components are produced by alternative splicing at the shaker locus in Drosophila

  1988cited by this paper
• Multiple potassium–channel components are produced by alternative splicing at the Shaker locus in Drosophila

  1988cited by this paper
• Multiple products of the Drosophila Shaker gene may contribute to potassium channel diversity.

  1988cited by this paper
• Data transformations for improved display and fitting of single-channel dwell time histograms.

  1987cited by this paper
• Statistical analysis of single sodium channels. Effects of N-bromoacetamide.

  1984influential reference
• Fitting and Statistical Analysis of Single-Channel Records

  1983cited by this paper
• Inactivation of the sodium channel. I. Sodium current experiments

  1977cited by this paper
• Inactivation of the sodium channel. II. Gating current experiments

  1977cited by this paper

• Closed State Structure of the Pore Revealed by Uncoupled Shaker K+ Channel

  2025cites this paper
• Concatenated Modular BK Channel Constructs Reveal Divergent Stoichiometry in Gating Control by LRRC26 (γ1), Pore, and Selectivity Filter

  2025cites this paper
• Closed State Structure of the Pore Revealed by Uncoupled Shaker K+ Channel

  2025cites this paper
• CryoEM structures of Kv1.2 potassium channels, conducting and non-conducting

  2025influential citation
• Energy landscape of a Kv channel revealed by temperature steps while perturbing its electromechanical coupling

  2025cites this paper
• Closed state structure of the pore revealed by uncoupled Shaker K+ channel

  2025cites this paper
• Electrically silent mutants unravel the mechanism of binding-gating coupling in Cys-loop receptors.

  2024cites this paper
• From resting state to inactivation: the dynamic journey of the inactivation peptide in Shaker Kv channels

  2024cites this paper
• Stability of N-type inactivation and the coupling between N-type and C-type inactivation in the Aplysia Kv1 channel

  2024cites this paper
• Turning a Kv channel into hot and cold receptor by perturbing its electromechanical coupling

  2024cites this paper
• Dilation of ion selectivity filters in cation channels.

  2024cites this paper
• PUFA stabilizes a conductive state of the selectivity filter in IKs channels

  2024cites this paper
• Isoleucine gate blocks K+ conduction in C-type inactivation

  2024cites this paper
• Inactivation of the Kv2.1 channel through electromechanical coupling

  2023cites this paper
• Eukaryotic Kv channel Shaker inactivates through selectivity filter dilation rather than collapse

  2023cites this paper
• Mechanism of external K+ sensitivity of KCNQ1 channels

  2023cites this paper
• Cryo-EM structures of Kv1.2 potassium channels, conducting and non-conducting

  2023influential citation
• A Mechanistic Reinterpretation of Fast Inactivation in Voltage-Gated Na+ Channels

  2023cites this paper
• A Mechanistic Reinterpretation of Fast Inactivation in Voltage-Gated Na+ Channels

  2023cites this paper
• Molecular rearrangements in S6 during slow inactivation in Shaker-IR potassium channels

  2023cites this paper
• A mechanistic reinterpretation of fast inactivation in voltage-gated Na+ channels

  2023cites this paper
• Allosteric coupling between transmembrane segment 4 and the selectivity filter of TALK1 potassium channels regulates their gating by extracellular pH

  2022cites this paper
• Kv1 channel inactivation: Slow and slower

  2022cites this paper
• Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators

  2022cites this paper
• The nonconducting W434F mutant adopts upon membrane depolarization an inactivated-like state that differs from wild-type Shaker-IR potassium channels

  2022cites this paper
• The 70‐year search for the voltage‐sensing mechanism of ion channels

  2022cites this paper
• Mutations within the selectivity filter reveal that Kv1 channels have distinct propensities to slow inactivate

  2022influential citation
• When Is a Potassium Channel Not a Potassium Channel?

  2022cites this paper
• Mechanisms Underlying C-type Inactivation in Kv Channels: Lessons From Structures of Human Kv1.3 and Fly Shaker-IR Channels

  2022cites this paper
• Structure of the Shaker Kv channel and mechanism of slow C-type inactivation

  2021influential citation
• Computational study of non-conductive selectivity filter conformations and C-type inactivation in a voltage-dependent potassium channel

  2021influential citation
• Structural basis for C-type inactivation in a Shaker family voltage-gated K+ channel

  2021cites this paper
• Regulation of K+ Conductance by a Hydrogen Bond in Kv2.1, Kv2.2, and Kv1.2 Channels

  2021cites this paper
• High-Resolution Structures of K+ Channels.

  2021cites this paper
• Experimental challenges in ion channel research: uncovering basic principles of permeation and gating in potassium channels

  2021cites this paper
• Structural Snapshots of Intermediates in the Gating of a K+ Channel.

  2021cites this paper
• Molecular basis for functional connectivity between the voltage sensor and the selectivity filter gate in Shaker K+ channels

  2021influential citation
• A unique mechanism of inactivation gating of the Kv channel family member Kv7.1 and its modulation by PIP2 and calmodulin

  2020cites this paper
• Functional consequences of two critical point mutations in the skeletal muscle excitation-contraction coupling complex

  2020cites this paper
• Familial neonatal seizures caused by the Kv7.3 selectivity filter mutation T313I

  2020cites this paper
• Noncanonical mechanism of voltage sensor coupling to pore revealed by tandem dimers of Shaker

  2019cites this paper
• KV1.2 channels inactivate through a mechanism similar to C-type inactivation

  2019cites this paper
• The interaction between the voltage-gated potassium channel h K v 1 . 3 and verapamil

  2018cites this paper
• Molecular mechanism of depolarization-dependent inactivation in W366F mutant of Kv1.2

  2018cites this paper
• Cooperativity in proton sensing by PIP aquaporins

  2018cites this paper
• Site and Mechanism of Action of Resin Acids on Voltage-Gated Ion Channels

  2018cites this paper
• Functional analyses of heteromeric human PIEZO1 Channels

  2018cites this paper
• Molecular tuning of electroreception in sharks and skates

  2018cites this paper
• S4–S5 linker movement during activation and inactivation in voltage-gated K+ channels

  2018influential citation
• A facile approach for the in vitro assembly of multimeric membrane transport proteins

  2018cites this paper
• The C-terminal HRET sequence of Kv1.3 regulates gating rather than targeting of Kv1.3 to the plasma membrane

  2018cites this paper
• Gating currents

  2018cites this paper
• Inactivation gating of Kv7.1 channels does not involve concerted cooperative subunit interactions

  2018cites this paper
• Single-particle cryo-EM structure of a voltage-activated potassium channel in lipid nanodiscs

  2018cites this paper
• Crystal structure of an inactivated mutant mammalian voltage-gated K+ channel

  2017cites this paper
• Intramolecular interactions that control voltage sensitivity in the jShak1 potassium channel from Polyorchis penicillatus

  2017cites this paper
• A glimpse into the C-type-inactivated state for a Potassium Channel

  2017cites this paper
• Atomic mutagenesis in ion channels with engineered stoichiometry

  2016cites this paper
• Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation

  2016cites this paper
• K+ Channel's Equilibrium Preference Reveals the Origin of Its Conduction Selectivity and the Inactivated State of the Selectivity Filter

  2016cites this paper
• Closed state-coupled C-type inactivation in BK channels

  2016cites this paper
• Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating.

  2016cites this paper
• A Disease Mutation Causing Episodic Ataxia Type I in the S1 Links Directly to the Voltage Sensor and the Selectivity Filter in Kv Channels

  2015influential citation
• Handbook of ion channels

  2015cites this paper
• Ion-binding properties of a K+ channel selectivity filter in different conformations

  2015cites this paper
• Modulation of Closed−State Inactivation in Kv2.1/Kv6.4 Heterotetramers as Mechanism for 4−AP Induced Potentiation

  2015cites this paper
• Stoichiometry of altered hERG1 channel gating by small molecule activators

  2014cites this paper
• Cooperative subunit interactions mediate fast C‐type inactivation of hERG1 K+ channels

  2014cites this paper
• Concerted All-or-none Subunit Interactions Mediate Slow Deactivation of Human ether-à-go-go-related Gene K+ Channels*

  2014cites this paper
• Moving gating charges through the gating pore in a Kv channel voltage sensor

  2014cites this paper
• A self-consistent approach for determining pairwise interactions that underlie channel activation

  2014cites this paper
• Structure and function of the thermoTRP channel pore.

  2014cites this paper
• K+ channel gating: C-type inactivation is enhanced by calcium or lanthanum outside

  2014cites this paper
• MOLECULAR MECHANISMS FOR PHOSPHOINOSITIDE REGULATION OF CONE PHOTORECEPTOR CNG CHANNEL GATING

  2014cites this paper
• Inter-Subunit Interactions across the Upper Voltage Sensing-Pore Domain Interface Contribute to the Concerted Pore Opening Transition of Kv Channels

  2013cites this paper
• S3-S4 linker length modulates the relaxed state of a voltage-gated potassium channel.

  2013cites this paper
• C-type inactivation of voltage-gated K+ channels: Pore constriction or dilation?

  2013cites this paper
• External Ba(2+) block of Kv4.2 channels is enhanced in the closed-inactivated state.

  2013cites this paper
• Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels

  2013influential citation
• Dynamics of internal pore opening in KV channels probed by a fluorescent unnatural amino acid

  2013cites this paper
• Pore Helices Play a Dynamic Role as Integrators of Domain Motion during Kv11.1 Channel Inactivation Gating*

  2013cites this paper
• A gating charge interaction required for late slow inactivation of the bacterial sodium channel NavAb

  2013cites this paper
• Mechanism of Cd2+ coordination during slow inactivation in potassium channels.

  2012cites this paper
• Human ether-a-go-go-related gene channel blockers and its structural analysis for drug design.

  2012cites this paper
• KCNQ1 Channels Do Not Undergo Concerted but Sequential Gating Transitions in Both the Absence and the Presence of KCNE1 Protein*

  2012cites this paper
• Structural changes of the outer and inner vestibule of hKv1.3 channels during C type inactivation

  2012cites this paper
• Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor

  2012cites this paper
• Initial steps in the opening of a Shaker potassium channel

  2012cites this paper
• Structural correlates of selectivity and inactivation in potassium channels.

  2012cites this paper
• Dual Effect of Phosphatidyl (4,5)-Bisphosphate PIP2 on Shaker K+ Channels*

  2012cites this paper
• Molecular mechanism for depolarization-induced modulation of Kv channel closure

  2012cites this paper
• A multipoint hydrogen-bond network underlying KcsA C-type inactivation.

  2011cites this paper
• Mode shift of the voltage sensors in Shaker K+ channels is caused by energetic coupling to the pore domain

  2011cites this paper
• ShakerIR and Kv1.5 mutant channels with enhanced slow inactivation also exhibit K+o-dependent resting inactivation

  2011cites this paper
• What's in gating currents? Going beyond the voltage sensor movement.

  2011cites this paper
• The influence of different lipid environments on the structure and function of the hepatitis C virus p7 ion channel protein

  2011cites this paper
• Uncoupling Charge Movement from Channel Opening in Voltage-gated Potassium Channels by Ruthenium Complexes*

  2011cites this paper
• Blockade of permeation by potassium but normal gating of the G628S nonconducting hERG channel mutant.

  2011cites this paper
• An Intersubunit Interaction between S4-S5 Linker and S6 Is Responsible for the Slow Off-gating Component in Shaker K+ Channels*

  2010cites this paper
• An examination of the slow inactivation and resting inactivation of Kv1.5 and ShakerIR

  2010influential citation