Uncoupling Charge Movement from Channel Opening in Voltage-gated Potassium Channels by Ruthenium Complexes*

The Kv2.1 channel generates a delayed-rectifier current in neurons and is responsible for modulation of neuronal spike frequency and membrane repolarization in pancreatic β-cells and cardiomyocytes. As with other tetrameric voltage-activated K+-channels, it has been proposed that each of the four Kv2.1 voltage-sensing domains activates independently upon depolarization, leading to a final concerted transition that causes channel opening. The mechanism by which voltage-sensor activation is coupled to the gating of the pore is still not understood. Here we show that the carbon-monoxide releasing molecule 2 (CORM-2) is an allosteric inhibitor of the Kv2.1 channel and that its inhibitory properties derive from the CORM-2 ability to largely reduce the voltage dependence of the opening transition, uncoupling voltage-sensor activation from the concerted opening transition. We additionally demonstrate that CORM-2 modulates Shaker K+-channels in a similar manner. Our data suggest that the mechanism of inhibition by CORM-2 may be common to voltage-activated channels and that this compound should be a useful tool for understanding the mechanisms of electromechanical coupling.

• Publication year

  2011

• Venue

  Journal of Biological Chemistry

• Publication date

  2011-03-17

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.M110.198010PMID 21454671PMCID PMC3091247
• 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.

• Calculation of the gating charge for the Kv1.2 voltage-activated potassium channel.

  2010cited by this paper
• Local Anesthetics Disrupt Energetic Coupling between the Voltage-sensing Segments of a Sodium Channel

  2009cited by this paper
• Carbon monoxide is a rapid modulator of recombinant and native P2X2 ligand‐gated ion channels

  2009cited by this paper
• Two Separate Interfaces between the Voltage Sensor and Pore Are Required for the Function of Voltage-Dependent K+ Channels

  2009cited by this paper
• The RCK1 high-affinity Ca2+ sensor confers carbon monoxide sensitivity to Slo1 BK channels

  2008cited by this paper
• Kv Channel Gating Requires a Compatible S4-S5 Linker and Bottom Part of S6, Constrained by Non-interacting Residues

  2008cited by this paper
• Functional analysis of Kv1.2 and paddle chimera Kv channels in planar lipid bilayers.

  2008cited by this paper
• Portability of paddle motif function and pharmacology in voltage sensors

  2007cited by this paper
• Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment

  2007cited by this paper
• The last few frames of the voltage-gating movie.

  2007cited by this paper
• 4-Aminopyridine Prevents the Conformational Changes Associated with P/C-Type Inactivation in Shaker Channels

  2007cited by this paper
• Photochemistry of trans‐ and cis‐[RuCl2(dmso)4] in Aqueous and Nonaqueous Solutions

  2007cited by this paper
• Binding of a Gating Modifier Toxin Induces Intersubunit Cooperativity Early in the Shaker K Channel's Activation Pathway

  2006cited by this paper
• Dissecting the coupling between the voltage sensor and pore domains.

  2006cited by this paper
• Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.

  2006cited by this paper
• How does voltage open an ion channel?

  2006cited by this paper
• PatchDock and SymmDock: servers for rigid and symmetric docking

  2005cited by this paper
• The S4 voltage sensor packs against the pore domain in the KAT1 voltage-gated potassium channel.

  2005cited by this paper
• Voltage-sensor activation with a tarantula toxin as cargo

  2005cited by this paper
• The Cooperative Voltage Sensor Motion that Gates a Potassium Channel

  2005cited by this paper
• Voltage Sensor of Kv1.2: Structural Basis of Electromechanical Coupling

  2005cited by this paper
• Molecular Compatibility of the Channel Gate and the N Terminus of S5 Segment for Voltage-gated Channel Activity*

  2005cited by this paper
• Voltage-gated ion channels

  2005cited by this paper
• Conserved gating hinge in ligand- and voltage-dependent K+ channels.

  2004cited by this paper
• Can Shaker Potassium Channels be Locked in the Deactivated State?

  2004cited by this paper
• Hemoxygenase-2 Is an Oxygen Sensor for a Calcium-Sensitive Potassium Channel

  2004cited by this paper
• Rate-limiting Reactions Determining Different Activation Kinetics of Kv1.2and Kv2.1 Channels

  2004cited by this paper
• Interaction between extracellular Hanatoxin and the resting conformation of the voltage-sensor paddle in Kv channels.

  2003cited by this paper
• Constitutive Activation of the Shaker Kv Channel

  2003cited by this paper
• Interactions between S4-S5 Linker and S6 Transmembrane Domain Modulate Gating of HERG K+ Channels*

  2002cited by this paper
• Coupling between Voltage Sensors and Activation Gate in Voltage-gated K+ Channels

  2002cited by this paper
• Dissecting intersubunit contacts in cyclic nucleotide-gated ion channels.

  2002cited by this paper
• Efficient Unbound Docking of Rigid Molecules

  2002cited by this paper
• Carbon Monoxide-Releasing Molecules: Characterization of Biochemical and Vascular Activities

  2002cited by this paper
• A model for 4-aminopyridine action on K channels: similarities to tetraethylammonium ion action.

  2001cited by this paper
• Ion conduction pore is conserved among potassium channels

  2001cited by this paper
• α-Helical Structural Elements within the Voltage-Sensing Domains of a K+ Channel

  2000cited by this paper
• A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.

  2000cited by this paper
• Mutations in the S4 Region Isolate the Final Voltage-dependent Cooperative Step in Potassium Channel Activation

  1999cited by this paper
• Voltage Sensitivity and Gating Charge in Shaker and Shab Family Potassium Channels

  1999cited by this paper
• Determinants of Voltage-Dependent Gating and Open-State Stability in the S5 Segment of Shaker Potassium Channels

  1999cited by this paper
• Inactivation of Kv2.1 potassium channels.

  1998cited by this paper
• Uncharged S4 Residues and Cooperativity in Voltage-dependent Potassium Channel Activation

  1998cited by this paper
• Single‐Channel Recording

  1998cited by this paper
• Structural conservation in prokaryotic and eukaryotic potassium channels.

  1998cited by this paper
• Role of the S4 in Cooperativity of Voltage-dependent Potassium Channel Activation

  1998cited by this paper
• Activation of Shaker Potassium Channels

  1998cited by this paper
• Activation of Shaker Potassium Channels

  1998cited by this paper
• Role of Transmembrane Segment S5 on Gating of Voltage-dependent K+ Channels

  1997cited by this paper
• Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites.

  1997cited by this paper
• How Does the W434F Mutation Block Current in Shaker Potassium Channels?

  1997cited by this paper
• Contribution of the S4 segment to gating charge in the Shaker K+ channel.

  1996cited by this paper
• N-type inactivation and the S4-S5 region of the Shaker K+ channel

  1996cited by this paper
• Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.

  1996cited by this paper
• Carbonyl Derivatives of Chloride-Dimethyl Sulfoxide-Ruthenium(II) Complexes: Synthesis, Structural Characterization, and Reactivity of Ru(CO)x(DMSO)4-xCl2 Complexes (x = 1-3)

  1995cited by this paper
• Shaker potassium channel gating. III: Evaluation of kinetic models for activation

  1994cited by this paper
• Gating of Shaker K+ channels: II. The components of gating currents and a model of channel activation.

  1994cited by this paper
• Shaker potassium channel gating. II: Transitions in the activation pathway

  1994cited by this paper
• Internal Na+ and Mg2+ blockade of DRK1 (Kv2.1) potassium channels expressed in Xenopus oocytes. Inward rectification of a delayed rectifier

  1994cited by this paper
• S4 mutations alter the single-channel gating kinetics of Shaker K+ channels.

  1993cited by this paper
• Gating currents from a nonconducting mutant reveal open-closed conformations in Shaker K+ channels.

  1993cited by this paper
• Gating currents of the cloned delayed-rectifier K+ channel DRK1.

  1993cited by this paper
• Maintenance of Xenopus laevis and oocyte injection.

  1992cited by this paper
• Nonstationary noise analysis and application to patch clamp recordings.

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

  1992cited by this paper
• [52] Analysis of nonstationary single-channel currents

  1992cited by this paper
• Ion channels. Analysis of nonstationary single-channel currents.

  1992cited by this paper
• The size of gating charge in wild-type and mutant Shaker potassium channels.

  1992cited by this paper
• cis- and trans-dihalotetrakis(dimethyl sulfoxide)ruthenium(II) complexes (RuX2(DMSO)4; X=Cl, Br): synthesis, structure, and antitumor activity

  1988cited by this paper
• The variance of sodium current fluctuations at the node of Ranvier

  1980cited by this paper
• Interaction of Tetraethylammonium Ion Derivatives with the Potassium Channels of Giant Axons

  1971cited by this paper

• Carbon Monoxide Signaling: Examining Its Engagement with Various Molecular Targets in the Context of Binding Affinity, Concentration, and Biologic Response

  2022cites this paper
• Mapping Electromechanical Coupling Pathways in Voltage-Gated Ion Channels: Challenges and the Way Forward

  2021cites this paper
• EVAP: A two-photon imaging tool to study conformational changes in endogenous Kv2 channels in live tissues

  2021cites this paper
• The AMIGO1 adhesion protein activates Kv2.1 voltage sensors

  2021cites this paper
• Kv2.1 channels play opposing roles in regulating membrane potential, Ca2+ channel function, and myogenic tone in arterial smooth muscle

  2020cites this paper
• An imaging method to measure conformational changes of voltage sensors of endogenous ion channels in tissue

  2019cites this paper
• Optical measurement of voltage sensing by endogenous ion channels

  2019cites this paper
• Optical measurement of endogenous ion channel voltage sensor activation in tissue

  2019cites this paper
• The tarantula toxin GxTx detains K+ channel gating charges in their resting conformation

  2018influential citation
• Gas Signaling Molecules and Mitochondrial Potassium Channels

  2018cites this paper
• Carbon monoxide releasing molecule-2 inhibition of snake venom thrombin-like activity: novel biochemical “brake”?

  2017cites this paper
• Gasotransmitter Heterocellular Signaling

  2017cites this paper
• Direct Inhibitory Effects of Carbon Monoxide on Six Venoms Containing Fibrinogenolytic Metalloproteinases

  2017cites this paper
• CO‐independent modification of K+ channels by tricarbonyldichlororuthenium(II) dimer (CORM‐2)

  2017cites this paper
• Carbon monoxide attenuates the effects of snake venoms containing metalloproteinases with fibrinogenase or thrombin-like activity on plasmatic coagulation

  2016cites this paper
• Carbon monoxide modulates electrical activity of murine myocardium via cGMP-dependent mechanisms

  2015cites this paper
• Alkanols inhibit voltage-gated K+ channels via a distinct gating modifying mechanism that prevents gate opening

  2015cites this paper
• NAMI-A is highly cytotoxic toward leukaemia cell lines: evidence of inhibition of KCa 3.1 channels.

  2014cites this paper
• Allosteric Coupling and Thermal Activation in TRP Channels

  2014cites this paper
• Carbon monoxide-based therapy ameliorates acute pancreatitis via TLR4 inhibition.

  2014cites this paper
• Resonance Energy Transfer Channel Determined by Fluorescence Ion Receptor Potential Vanilloid 1 (TRPV1) Coarse Architecture of the Transient

  2013cites this paper
• Coarse Architecture of the Transient Receptor Potential Vanilloid 1 (TRPV1) Ion Channel Determined by Fluorescence Resonance Energy Transfer*

  2013cites this paper
• Ru(CO)3Cl(Glycinate) (CORM-3): A Carbon Monoxide–Releasing Molecule with Broad-Spectrum Antimicrobial and Photosensitive Activities Against Respiration and Cation Transport in Escherichia coli

  2013cites this paper
• Divergent molecular mechanisms underlay CO- and CORM-2-induced relaxation of corpora cavernosa.

  2012cites this paper
• Carbon Monoxide–Sensitive Apoptotic Death of Erythrocytes

  2012cites this paper
• The Anti-Microbial Effects of Carbon Monoxide and Carbon Monoxide-Releasing Molecule-3 (CORM-3)

  2012cites this paper
• Carbon monoxide and outcome of stroke--a dream CORM true?.

  2012cites this paper
• Mechanism of Electromechanical Coupling in Voltage-Gated Potassium Channels

  2012cites this paper
• Carbon Monoxide Protects Against Ischemia-reperfusion Injury in Vitro via Antioxidant Properties

  2012cites this paper
• Gating Charge Movement in Native Cells: Another Application of the Patch Clamp Technique

  2012cites this paper
• Carbon monoxide: an emerging regulator of ion channels

  2011cites this paper