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Related Concept Videos

Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.

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Electro-Mechanical Uncoupling of K<sub>V</sub>7.1 Voltage Sensor and Pore by 1,4-Benzodiazepines Is Modulated by Decoration of Position 1.

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Related Experiment Video

Updated: Jun 6, 2026

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
08:33

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time

Published on: March 11, 2021

Structure-Activity Relationship Study on Ligands Activating the Voltage-Gated Potassium Channel KV7.1.

Florian Roßner1,2, Judith Schmidt2, Guiscard Seebohm1,3

  • 1GRK 2515, Chemical Biology of Ion Channels (Chembion), Universität Münster, Münster, Germany.

Archiv Der Pharmazie
|June 5, 2026
PubMed
Summary

Novel 1,4-benzodiazepines were synthesized and tested as potassium channel KV7.1 activators. The (3R)-configuration and indolylmethyl group are crucial for KV7.1 activation, with derivative 9i showing enhanced activity and metabolic stability.

Keywords:
1,4‐benzodiazepin‐2‐onesKV7.1 ion channelSugasawa reactionactivationchiral HPLClipophilicitymetabolic stabilitypharmacokinetic parametersstructure–activity relationshipstwo‐electrode voltage clamp

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Patch Clamp and Perfusion Techniques for Studying Ion Channels Expressed in Xenopus oocytes
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Patch Clamp and Perfusion Techniques for Studying Ion Channels Expressed in Xenopus oocytes

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Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels
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Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels

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Last Updated: Jun 6, 2026

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time
08:33

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time

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Patch Clamp and Perfusion Techniques for Studying Ion Channels Expressed in Xenopus oocytes
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Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels
11:19

Site Directed Spin Labeling and EPR Spectroscopic Studies of Pentameric Ligand-Gated Ion Channels

Published on: July 4, 2016

Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Ion Channel Modulation

Background:

  • Potassium channel KV7.1 activators are investigated for treating hypertension, arrhythmia, and preterm labor.
  • The 1,4-benzodiazepine (R)-L3 is a known potent KV7.1 activator, serving as a lead compound for further development.

Purpose of the Study:

  • To systematically modify the structure of (R)-L3 at eight positions, including the 3-position stereochemistry.
  • To synthesize and evaluate novel 1,4-benzodiazepine derivatives for KV7.1 channel activation.
  • To identify key structural features essential for potent KV7.1 agonistic activity and improved metabolic stability.

Main Methods:

  • Synthesis of 1,4-benzodiazepines via reaction of 2-aminobenzophenones with amino acid-derived oxazolidinediones.
  • Regioselective synthesis of 2-aminobenzophenones using the Sugasawa reaction.
  • Evaluation of ion channel activity using two-electrode voltage-clamp (TEVC) electrophysiology.
  • Chiral High-Performance Liquid Chromatography (HPLC) for enantiomer separation.

Main Results:

  • The (3R)-configuration and the 3-indolylmethyl moiety are essential for KV7.1 activation.
  • Secondary lactam 8b and methylated lactam 9b exhibited high KV7.1 activity, while larger N-substituents decreased activation.
  • The 9-hydroxy derivative 9i demonstrated significantly higher agonistic activity (+68%) and improved phase I metabolic stability compared to (R)-L3 (9b, +45%).
  • Replacement of the 2-fluoro substituent on the phenyl ring reduced KV7.1 activity.

Conclusions:

  • Structural modifications confirm the importance of the (3R)-configuration and the indolylmethyl group for KV7.1 activation.
  • Derivative 9i represents a promising KV7.1 activator with enhanced potency and metabolic stability, warranting further investigation for therapeutic applications.