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Related Concept Videos

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.
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.
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...
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

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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Related Experiment Video

Updated: May 11, 2026

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
08:27

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

Published on: January 7, 2019

Conserved gating elements in TRPC4 and TRPC5 channels.

Andreas Beck1, Tilman Speicher, Christof Stoerger

  • 1Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany. andreas.beck@uniklinikum-saarland.de

The Journal of Biological Chemistry
|May 17, 2013
PubMed
Summary
This summary is machine-generated.

Mutations in TRPC4 and TRPC5 ion channels, specifically within the S4-S5 linker, lead to constitutive opening and cell death. This suggests the linker is crucial for TRPC channel gating regulation.

Keywords:
Calcium ImagingCalcium InfluxChannel GatingIon ChannelsPatch ClampSignal TransductionTRP Channels

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Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
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Purification of Endogenous Drosophila Transient Receptor Potential Channels

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Area of Science:

  • Molecular biology
  • Ion channel physiology
  • Cell signaling

Background:

  • Transient Receptor Potential Canonical (TRPC) 4 and TRPC5 proteins are nonselective cation channels permeable to calcium (Ca2+).
  • These channels are activated by receptors linked to phosphoinositide signaling cascades.
  • The S4-S5 linker region is known to play a role in ion channel function.

Purpose of the Study:

  • To investigate the role of the S4-S5 linker in the gating mechanism of TRPC4 and TRPC5 ion channels.
  • To determine the effect of specific mutations within the S4-S5 linker on channel activity and cellular function.

Main Methods:

  • Site-directed mutagenesis was used to introduce specific amino acid substitutions (Glycine to Serine) in the S4-S5 linker of TRPC4 and TRPC5.
  • Electrophysiological recordings (current-voltage relationships) were performed to analyze ion channel activity.
  • Cell viability assays were conducted to assess the impact of mutant channel expression on cells.
  • Structural modeling was employed to predict potential interaction sites within the channel.

Main Results:

  • A mutation (G503S in TRPC4, G504S in TRPC5) in the S4-S5 linker resulted in constitutive channel opening.
  • Expression of these mutants led to cell death, which was preventable by Ca2+ buffering.
  • Mutant channel activity resembled fully activated wild-type channels.
  • A second mutation (S623A) in TRPC4G503S suppressed constitutive activation and partially restored function, suggesting an interaction site within the S6 helix.

Conclusions:

  • The S4-S5 linker is a critical component of TRPC4 and TRPC5 channel gating.
  • Alterations in the S4-S5 linker sequence can lead to channel opening independent of upstream signaling.
  • These findings provide insights into the molecular mechanisms underlying TRPC channel regulation.