Video Experimental Relacionado
Updated: Jul 29, 2026
13:40
Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
Published on: July 7, 2011
Identificación de un sitio en las subunidades del receptor de glutamato que controla la permeabilidad del calcio
R I Hume1, R Dingledine, S F Heinemann
1Molecular Neurobiology Laboratory, Salk Institute, La Jolla, CA 92037.
Science (New York, N.Y.)
|August 30, 1991
Resumen
Los investigadores identificaron un sitio clave en los receptores de glutamato no N-metil-D-aspartato (no NMDA) que controla la permeabilidad del calcio. La alteración de la carga en este sitio modifica el flujo de iones y la función del receptor, revelando determinantes estructurales de las propiedades del canal.
Área de la Ciencia:
- La neurociencia es la neurociencia.
- Biología Molecular Biología Molecular
- La bioquímica es la bioquímica.
Sus antecedentes:
- El glutamato es un neurotransmisor excitatorio primario en el cerebro.
- Los receptores no N-metil-D-aspartato (no NMDA) son canales iónicos ligandos cruciales.
- Las diferentes combinaciones de subunidades de los receptores no NMDA exhiben una permeabilidad al calcio variable.
Objetivo del estudio:
- Para investigar las bases estructurales de la permeación iónica en los receptores de glutamato no NMDA.
- Para identificar residuos específicos de aminoácidos que regulan la permeabilidad del calcio y las relaciones de corriente-voltaje.
Principales métodos:
- Construcción y análisis de subunidades mutantes de los receptores no NMDA con sustituciones de un solo aminoácido.
- Registros electrofisiológicos para evaluar las relaciones corriente-tensión y la permeabilidad del calcio.
Principales resultados:
- Se identificó un sitio específico de aminoácidos que, cuando se muta para alterar la carga neta (por ejemplo, de glutamina a arginina), afecta significativamente la función del receptor.
- Los cambios en este sitio alteraron tanto la relación corriente-voltaje como la permeabilidad al calcio de los receptores no NMDA.
Conclusiones:
- Se ha identificado un sitio crítico que regula las propiedades de permeación iónica de los receptores de glutamato no NMDA.
- Este hallazgo proporciona información sobre los determinantes estructurales de la selectividad iónica y la apertura de canales en estos importantes receptores.
Videos de Conceptos Relacionados
00:49Ligand Binding and Linkage
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
01:19Ligand-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...
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...
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
01:27Feedback Regulation of Calcium Concentration
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:30Ligand-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...