Related Experiment Video

Updated: Oct 2, 2025

Recapitulation of an Ion Channel IV Curve Using Frequency Components
10:14

Recapitulation of an Ion Channel IV Curve Using Frequency Components

Published on: February 8, 2011

13.7K

Molecular dynamics simulations suggest possible activation and deactivation pathways in the hERG channel

Flavio Costa1, Carlo Guardiani1, Alberto Giacomello2

  • 1Dipartimento di Ingegneria Meccanica e Aerospaziale, Sapienza Università di Roma, Via Eudossiana 18, 00184, Rome, Italy.

Communications Biology
|February 25, 2022
PubMed

Insights

Investigating the human Ether-à-go-go-Related Gene (hERG) channel

Area of Science:

  • Biophysics
  • Molecular Biology
  • Cardiovascular Science

Background:

  • The human Ether-à-go-go-Related Gene (hERG) channel is crucial for cardiac electrical activity.
  • Dysfunction of hERG channels leads to Long QT Syndrome and other cardiac channelopathies.
  • Understanding hERG channel gating is vital for treating inherited and drug-induced arrhythmias.

Purpose of the Study:

  • To elucidate the activation/deactivation mechanism of the hERG channel.
  • To provide a structural model for the closed state of the hERG channel.
  • To identify molecular pathways involved in hERG channel gating and mutation effects.

Main Methods:

  • Homology modeling to create a closed-state structure of the hERG channel.
  • Molecular dynamics simulations to analyze channel dynamics.
  • Network analysis to identify communication pathways within the channel.
  • Split-channel simulations to probe domain interactions.

Main Results:

  • Two distinct pathways connecting the voltage sensor and pore domains were identified.
  • hERG channel gating persists even when the voltage sensor domain is partially disconnected.
  • LQTS-associated mutations are located along the identified communication pathways, suggesting their role in gating disruption.

Conclusions:

  • The study proposes potential activation/deactivation mechanisms for non-domain-swapped potassium channels.
  • Findings offer insights into the molecular basis of Long QT Syndrome.
  • Results may inform the development of novel therapeutic strategies for cardiac channelopathies.

More Related Videos

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

8.8K
Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time08:33

Measuring Nucleotide Binding to Intact, Functional Membrane Proteins in Real Time

Published on: March 11, 2021

2.1K

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...
2.8K
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...
12.9K
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...
6.8K
Activation and Inactivation of G Proteins01:22

Activation 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...
7.9K
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several...
8.8K
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

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...
4.9K