Video Experimental Relacionado

Updated: Nov 9, 2025

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

La corriente de canal de sodio tardío cardíaco es un objetivo molecular para el inhibidor de sodio / glucosa 2

Koenraad Philippaert^1,2, Subha Kalyaanamoorthy^3,4, Mohammad Fatehi^1,2

¹Alberta Diabetes Institute (K.P., M.F., W.L., A.B., J.S., J.W., T.P., C.S., J.M.S., P.E.L.), University of Alberta, Edmonton, Canada.xs.

|April 9, 2021

Resumen

Los inhibidores del cotransportador de sodio-glucosa 2 (SGLT2) reducen la corriente tardía de sodio (Na) en modelos de insuficiencia cardíaca. Este hallazgo sugiere que los inhibidores de SGLT2 pueden ofrecer cardioprotección al dirigirse a esta corriente del canal de sodio cardíaco.

Área de la Ciencia:

Cardiología
Biología molecular
Farmacología

Sus antecedentes:

Los inhibidores del cotransportador de sodio-glucosa 2 (SGLT2) muestran efectos cardioprotectores significativos en pacientes diabéticos con insuficiencia cardíaca.
Los mecanismos moleculares precisos que subyacen a estos efectos cardioprotectores siguen siendo objeto de investigación.
El componente tardío de la corriente del canal de sodio cardíaco (Na) está implicado en la fisiopatología de la insuficiencia cardíaca.

Objetivo del estudio:

Investigar si los inhibidores de SGLT2 pueden inhibir el componente tardío de la corriente del canal de sodio cardíaco (Na tardío).
Explorar los posibles mecanismos moleculares mediante los cuales los inhibidores de SGLT2 ejercen cardioprotección.

Principales métodos:

Estudios electrofisiológicos en cardiomiocitos.
En las simulaciones de acoplamiento molecular de silicio.
Imágenes de calcio y técnicas de perfusión de todo el corazón.

Principales resultados:

La empagliflozina, un inhibidor de SGLT2, redujo significativamente el late-I< sub>Na en los cardiomiocitos de ratón y en los canales Nav1.5 con mutaciones específicas.
La empagliflozina, la dapagliflozina y la canagliflozina inhibían selectivamente el H₂2 inducido por la I_Na tardía sin afectar el pico de la corriente de sodio.
La unión de empagliflozina a Nav1.5 ocurre en una región similar a la de los anestésicos locales y la ranolazina, y previno la activación del inflamatorio y mejoró la función cardíaca después de la isquemia.

Conclusiones:

Late-I_Na representa un objetivo molecular potencial para los inhibidores de SGLT2 en el corazón.
La inhibición del Na-I tardío puede contribuir a los efectos cardioprotectores de los inhibidores de SGLT2.
Estos hallazgos esclarecen un nuevo mecanismo para la cardioprotección mediada por inhibidores de SGLT2.

Palabras clave:

Inhibidores de la SGLT2 Canal de sodio cardíaco Perspectiva clínica Empagliflozina y sus derivados insuficiencia cardíaca

Más Videos Relacionados

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels

Published on: January 27, 2013

A Fluorescence-Based Assay of Membrane Potential for High-Throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines

A Fluorescence-Based Assay of Membrane Potential for High-Throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines

Published on: June 22, 2022

Videos de Conceptos Relacionados

Secondary Active Transport

Secondary Active Transport

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme “pump” embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...

Secondary Active Transport

Secondary Active Transport

One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...

Glucose Absorption Into the Small Intestine

Glucose Absorption Into the Small Intestine

Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...

Glucose Transporters

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:

Glucagon-like Receptor Agonists

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...

Transducer Mechanism: Enzyme-Linked Receptors

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: