Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

GPCR Desensitization01:12

GPCR Desensitization

5.6K
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...
5.6K
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

2.0K
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...
2.0K
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

1.4K
Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
1.4K
The Two-State Receptor Model01:29

The Two-State Receptor Model

1.8K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
1.8K
Opioid Receptors: Overview01:22

Opioid Receptors: Overview

332
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
332
The Role of Ion Channels in Neuronal Computation01:19

The Role of Ion Channels in Neuronal Computation

3.1K
A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
3.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Antimicrobial effects of compound Huangbai liquid on <i>staphylococcus aureus</i>, <i>Escherichia coli</i> and MRSA: clinical, bacterial, and animal experimental studies.

American journal of translational research·2026
Same author

Structural Basis of Inhibition and Desensitization in Heteromeric Kainate Receptors.

bioRxiv : the preprint server for biology·2026
Same author

Structural insights into kainate receptor desensitization.

Nature communications·2025
Same author

Periaortic lymphatic vessels protect against thoracic aortic dissection through mobilizing immune response.

Cardiovascular research·2025
Same author

Structural basis of GluK2 kainate receptor activation by a partial agonist.

Nature structural & molecular biology·2025
Same author

Endothelial Myosin IIA Is Required for the Maintenance of Blood-Brain Barrier Integrity.

Cells·2024
Same journal

Layered social competition coordinates reproductive hierarchy formation in ants.

bioRxiv : the preprint server for biology·2026
Same journal

Combination epigenetic-targeted therapy increases the immunogenicity of poorly immunogenic sarcomas.

bioRxiv : the preprint server for biology·2026
Same journal

Loss of LanC-like proteins delays post-injury regeneration of aging skeletal muscles.

bioRxiv : the preprint server for biology·2026
Same journal

Integrative Transfer Network: Deep Transfer Learning Across Populations and Prediction Targets.

bioRxiv : the preprint server for biology·2026
Same journal

Confidence-supported label-free metabolic imaging with FPhaS phase autofluorescence microscopy.

bioRxiv : the preprint server for biology·2026
Same journal

Sequence-encoded autoinhibition couples mRNA decapping activity to phase separation.

bioRxiv : the preprint server for biology·2026
See all related articles

Related Experiment Video

Updated: May 13, 2025

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

10.6K

Structural Insights into Kainate Receptor Desensitization.

Changping Zhou1,2, Guadalupe Segura-Covarrubias1,2, Nami Tajima1

  • 1Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Ohio, 44106, USA.

Biorxiv : the Preprint Server for Biology
|April 16, 2025
PubMed
Summary
This summary is machine-generated.

Kainate receptors (KARs) undergo unique conformational changes during desensitization, unlike other ionotropic glutamate receptors (iGluRs). Structural and functional data reveal that KAR ligand-binding domain rotation is crucial for complete channel closure and distinct desensitization mechanisms.

Keywords:
Kainate-type ionotropic glutamate receptorsdesensitization mechanismstructure

More Related Videos

Purification and Reconstitution of TRPV1 for Spectroscopic Analysis
11:53

Purification and Reconstitution of TRPV1 for Spectroscopic Analysis

Published on: July 3, 2018

7.9K
Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
15:28

Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells

Published on: October 1, 2010

17.4K

Related Experiment Videos

Last Updated: May 13, 2025

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

10.6K
Purification and Reconstitution of TRPV1 for Spectroscopic Analysis
11:53

Purification and Reconstitution of TRPV1 for Spectroscopic Analysis

Published on: July 3, 2018

7.9K
Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
15:28

Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells

Published on: October 1, 2010

17.4K

Area of Science:

  • Neuroscience
  • Structural Biology
  • Molecular Pharmacology

Background:

  • Kainate receptors (KARs) are ionotropic glutamate receptors (iGluRs) vital for excitatory neurotransmission in the central nervous system.
  • Receptor desensitization modulates synaptic transmission strength and plasticity, but KAR desensitization mechanisms remain distinct from other iGluRs like AMPA receptors.
  • A key unresolved question is why KARs require large conformational changes for desensitization, unlike their AMPA receptor counterparts.

Purpose of the Study:

  • To elucidate the unique mechanism and conformational dynamics of kainate receptor desensitization.
  • To investigate the structural basis for the distinct desensitization process in KARs compared to other iGluRs.
  • To understand the role of ligand-binding domain (LBD) movements in KAR channel gating and pore closure.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to determine structures of GluK2 KARs in non-desensitized, shallow-desensitized, and deep-desensitized states.
  • Engineered double cysteine mutations and crosslinking were employed to stabilize specific receptor conformations.
  • Patch-clamp electrophysiology and fluctuation analysis were performed to assess ion permeability and desensitization kinetics.

Main Results:

  • Cryo-EM structures revealed multiple KAR conformations, including a shallow-desensitized state with an incompletely closed channel pore.
  • Engineered crosslinks stabilized KARs in conformations resembling AMPA receptor desensitization but with retained ion permeability.
  • Electrophysiological data showed that shallow-desensitized KARs remain conductive, indicating incomplete pore closure.

Conclusions:

  • The lateral rotational movement of KAR ligand-binding domains is essential for complete channel closure during desensitization.
  • This large conformational change distinguishes KAR desensitization from that of other iGluRs, explaining their unique gating properties.
  • The study defines the unique mechanism and conformational dynamics underlying KAR desensitization, advancing our understanding of synaptic transmission.