Related Experiment Video
Updated: Dec 15, 2025
10:22
Reconstitution of a Kv Channel into Lipid Membranes for Structural and Functional Studies
Published on: July 13, 2013
19.8K
Modulation of KV7 Channel Deactivation by PI(4,5)P2.
1Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA, United States.
Frontiers in Pharmacology
|July 9, 2020
Summary
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) depletion affects KV7.2/KV7.3 channel deactivation kinetics. PI(4,5)P2 levels influence channel stabilization and Retigabine sensitivity, particularly after prolonged activation.
Area of Science:
- Neuroscience
- Molecular Biology
- Biophysics
Background:
- KV7 channels regulate cellular electrical excitability.
- Heteromeric KV7.2/KV7.3 channels generate M-currents, inhibited by Gq protein-coupled receptors.
- Gq protein-coupled receptor activation reduces PI(4,5)P2, essential for KV7 channel function.
Purpose of the Study:
- To investigate the impact of PI(4,5)P2 depletion on KV7.2/KV7.3 channel modal behavior.
- To test the hypothesis that PI(4,5)P2 depletion hinders activated channel stabilization, increasing deactivation rates.
Main Methods:
- Co-expression of KV7.2/KV7.3 channels with Ci-VS-TPIP (a phosphoinositide phosphatase).
- Treatment of cells with Wortmannin, a phosphoinositide kinase inhibitor, to deplete PI(4,5)P2.
- Analysis of channel deactivation kinetics and Retigabine sensitivity under varying activation durations.
Main Results:
- PI(4,5)P2 depletion via Ci-VS-TPIP or Wortmannin reduced the activity-dependent slowdown of KV7.2/KV7.3 channel deactivation.
- These effects were more pronounced following prolonged channel activation compared to short activation.
- PI(4,5)P2 depletion diminished Retigabine's effect on deactivation kinetics, especially after prolonged activation.
Conclusions:
- KV7.2/KV7.3 channel deactivation kinetics are sensitive to PI(4,5)P2 levels in an activation-dependent manner.
- Reduced PI(4,5)P2 levels impair the stabilization of the activated channel state, particularly during sustained activity.
- These findings elucidate the role of PI(4,5)P2 in KV7 channel gating and modal behavior.
Related Concept Videos
01:12Mechanically-gated Ion Channels
7.4K
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...
7.4K
01:26Voltage-gated Ion Channels
9.9K
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...
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...
9.9K
01:28Depolarizing Blockers: Mechanism of Action
2.4K
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
2.4K
01:19The Role of Ion Channels in Neuronal Computation
3.5K
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....
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....
3.5K
01:11IP3/DAG Signaling Pathway
13.9K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
13.9K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
3.5K
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...
3.5K