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Thermosensation01:43

Thermosensation

30.9K
Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
30.9K
Mechanically-gated Ion Channels01:12

Mechanically-gated Ion Channels

6.5K
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...
6.5K
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

2.4K
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...
2.4K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

4.7K
GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
4.7K
GPCR Desensitization01:12

GPCR Desensitization

6.2K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
6.2K
Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

12.6K
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...
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Related Experiment Video

Updated: Aug 12, 2025

Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
12:09

Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4

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Temperature-Sensitive Contact Modes Allosterically Gate TRPV3.

Dan Burns, Vincenzo Venditti, Davit A Potoyan

    Biorxiv : the Preprint Server for Biology
    |January 30, 2023
    PubMed
    Summary
    This summary is machine-generated.

    TRPV channels sense temperature through specific residue interactions. This study reveals how these interactions, analyzed via simulations and machine learning, control channel gating, offering insights into thermosensation.

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    Area of Science:

    • Molecular biology
    • Biophysics
    • Computational chemistry

    Background:

    • Transient Receptor Potential (TRPV) ion channels are crucial thermosensors.
    • Understanding the molecular basis of TRPV channel temperature gating is essential but remains challenging.
    • Cryo-electron microscopy (cryo-EM) has provided structural insights, but dynamic mechanisms are less understood.

    Approach:

    • Utilized molecular simulations, multi-ensemble contact analysis, graph theory, and machine learning.
    • Investigated temperature-sensitive residue-residue interactions driving allostery in TRPV3.
    • Analyzed changes in channel community structure and contact network centrality with temperature.

    Key Points:

    • Identified distinct clusters of residues with temperature-dependent contact profiles, including a dominant mode on the ankyrin repeat domain.
    • Revealed a temperature-sensitive contact network connecting distant channel regions to the gate, mediating allosteric regulation.
    • Demonstrated that specific temperature-sensitive contact modes predict the channel gate's state using a random forest model.

    Conclusions:

    • Elucidated high-resolution molecular mechanisms of temperature sensing and allosteric gating in TRPV channels.
    • Validated findings through identification of functionally critical residues reported in existing literature.
    • Highlighted the utility of temperature-sensitive contact analysis for understanding ion channel dynamics and function.