Related Experiment Video
Updated: Jul 13, 2026
11:33
Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
Published on: March 12, 2013
The aromatic cluster in KCHIP1b affects Kv4 inactivation gating.
D Van Hoorick1, A Raes, D J Snyders
1Laboratory for Molecular Biophysics, Physiology and Pharmacology, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
The Journal of Physiology
|July 21, 2007
Summary
The KChIP1b splice variant slows Kv4.2 channel recovery. Replacing aromatic residues in KChIP1b with alanine converts this to fast KChIP1a-like recovery, revealing the aromatic cluster
Area of Science:
- Molecular biology
- Neuroscience
- Ion channel physiology
Background:
- Potassium channel interacting proteins (KChIPs) modulate Kv4 channel function.
- KChIP1 splice variants, KChIP1a and KChIP1b, differentially affect Kv4.2 channel gating.
- KChIP1b contains an exon1b with aromatic residues influencing Kv4.2 inactivation.
Purpose of the Study:
- To investigate the role of the KChIP1b aromatic cluster in modifying Kv4.2 channel gating.
- To determine how specific aromatic residues in KChIP1b contribute to slow inactivation recovery.
- To elucidate the mechanism by which KChIP1b alters Kv4.2 channel kinetics.
Main Methods:
- Site-directed mutagenesis of KChIP1b to substitute aromatic residues with alanine.
- Electrophysiological recordings (e.g., voltage-clamp) to analyze Kv4.2 channel gating.
- Comparative analysis of Kv4.2 gating properties with KChIP1a and KChIP1b variants.
Main Results:
- Substitution of aromatic residues in KChIP1b's exon1b partially or fully restored fast inactivation recovery kinetics to KChIP1a levels.
- Replacing three aromatic residues in KChIP1b mimicked KChIP1a's fast recovery.
- Mutations also affected closed-state inactivation and voltage dependence of inactivation, similar to KChIP1a.
Conclusions:
- The aromatic cluster in KChIP1b's exon1b is critical for inducing slow Kv4.2 inactivation recovery.
- Reducing the bulkiness of exon1b residues converts the KChIP1b phenotype to the KChIP1a phenotype.
- KChIP1b's aromatic residues modulate transitions to and from closed inactivated states of Kv4.2 channels.
Related Concept Videos
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...
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...
01:19Ligand-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...
01:21G-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 organs,...
Sensory organs,...
01:24Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
01:24Non-gated Ion Channels
Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.