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Related Concept Videos

Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

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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...
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The Role of Ion Channels in Neuronal Computation01:19

The Role of Ion Channels in Neuronal Computation

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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....
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Non-gated Ion Channels01:24

Non-gated Ion Channels

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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....
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Ligand-gated Ion Channels01:19

Ligand-gated Ion Channels

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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...
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Ion Channels01:19

Ion Channels

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The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
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Electrochemical Gradient and Channel Proteins: An Overview01:21

Electrochemical Gradient and Channel Proteins: An Overview

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An electrochemical gradient is a fundamental concept in biology and chemistry. It regulates the movement of ions across cell membranes. This movement is influenced by two factors:
The electrical gradient: The electrical gradient across cell membranes refers to the difference in electric charge between the inside and outside of a cell.  This difference drives the movement of ions towards or away from the cells. For instance, if the inside of the cell is more negatively charged relative to...
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Updated: May 10, 2025

Recapitulation of an Ion Channel IV Curve Using Frequency Components
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Recapitulation of an Ion Channel IV Curve Using Frequency Components

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Structural insights into the function, dysfunction and modulation of Kv3 channels.

Manuel Covarrubias1, Qiansheng Liang1, Linh Nguyen-Phuong1

  • 1Department of Neuroscience, Sidney Kimmel Medical College of Thomas Jefferson University, Bluemle Life Science Building, 233 South 10th Street, Room 231, Philadelphia, PA, 19107, USA; Vickie and Jack Farber Institute for Neuroscience, USA; Jefferson Synaptic Biology Center, USA.

Neuropharmacology
|April 27, 2025
PubMed
Summary
This summary is machine-generated.

Kv3 channels are crucial for rapid nerve signaling and function. Recent cryo-EM studies reveal their gating mechanisms, disease links, and modulation, offering insights into nervous system function and pain.

Keywords:
Cryo-EMKv channelKv channel gatingKv channel modulatorsPain modulation

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Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
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Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biophysics

Background:

  • Voltage-gated potassium (Kv) channels, specifically the Kv3 subfamily, play a critical role in neuronal excitability.
  • Kv3 channels are essential for fast action potential repolarization, influencing neuronal firing patterns and synaptic transmission.

Purpose of the Study:

  • To review and integrate recent cryo-electron microscopy (cryo-EM) studies on Kv3 channel function.
  • To elucidate the structural and mechanistic basis of Kv3 channel gating, dysfunction, and modulation.
  • To provide a perspective on Kv3 channel roles in the nervous system and pain modulation.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) for structural determination.
  • Functional studies to investigate channel gating and modulation.
  • Analysis of disease-associated variants and allosteric modulator mechanisms.

Main Results:

  • The cytoplasmic T1 domain of Kv3.1 channels has a surprising role in gating.
  • A Kv3.2 variant (C125Y) is linked to developmental epileptic encephalopathy.
  • Positive allosteric modulators interact with Kv3.1 and Kv3.2 channels through novel mechanisms.
  • Kv3.4 phosphorylation regulates spike broadening and synaptic facilitation.

Conclusions:

  • Kv3 channels are key regulators of neuronal excitability and synaptic function.
  • Structural insights are advancing our understanding of Kv3 channelopathies and therapeutic strategies.
  • Kv3 channel function is dynamically regulated by structural domains and post-translational modifications, impacting nervous system activity and pain.