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Related Concept Videos

Patch Clamp01:18

Patch Clamp

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Many fundamental cell functions such as muscle contraction and nerve transmission rely on the electrical signals produced by the movement of positively and negatively charged ions across the cell membrane. One competent method to record current flowing across the whole cell or single ion channel is the patch-clamp technique.
In this method, a glass micropipette containing electrolyte solution is tightly sealed against a small portion of the cell membrane. As a result, a patch of the cell...
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Voltage-gated Ion Channels01:26

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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.
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Ion Channels01:19

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The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
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Non-gated Ion Channels01:24

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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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Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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Updated: Sep 11, 2025

Reconstitution of a Kv Channel into Lipid Membranes for Structural and Functional Studies
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Discovery and In-Vivo Characterization of Kv7 Channel Openers through a Phenotypic Approach.

Romain Siegrist1, Olivier Bezençon1, Caroline Deymier1

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Summary

Researchers discovered a new class of urea compounds effective against epilepsy. Compound 31 shows promise as an orally bioavailable treatment by activating KV7 potassium channels, offering hope for uncontrolled seizures.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Drug Discovery

Background:

  • Epilepsy affects millions, with ~30% of patients unresponsive to current antiseizure drugs (ASDs).
  • Existing ASDs often exhibit polypharmacology, and polypharmacy is common in treatment.
  • Traditional drug discovery relied on animal models, posing ethical and technical challenges.

Purpose of the Study:

  • To develop an in vitro assay for identifying novel antiseizure compounds.
  • To discover a new class of compounds targeting neuronal hyperexcitability.
  • To identify and optimize a lead compound for epilepsy treatment.

Main Methods:

  • Development of an in vitro assay mimicking seizure-related neuronal hyperexcitability.
  • Phenotypic screening of compound libraries using the novel assay.
  • Lead optimization, pharmacokinetic profiling, in vivo efficacy testing in rodent epilepsy models, and target deconvolution.

Main Results:

  • Discovery of a novel class of urea compounds with antiseizure potential.
  • Identification of compound 31 (IDOR-1104-0086) as a lead candidate.
  • Compound 31 demonstrated oral bioavailability, brain penetration, in vivo efficacy, and a favorable tolerability profile.
  • Target deconvolution identified KV7 potassium channel activation as the mechanism of action.

Conclusions:

  • The developed in vitro assay is effective for unbiased discovery of antiseizure compounds.
  • Urea compounds, exemplified by compound 31, represent a promising new class of ASDs.
  • KV7 potassium channel activation is a viable mechanism for treating epilepsy, particularly in cases of uncontrolled seizures.