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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 types of...
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Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

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

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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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Regulation of Sodium and Potassium01:26

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The regulation of sodium and potassium ion concentrations in the human body is a complex process governed primarily by hormones such as aldosterone, antidiuretic hormone (ADH), and atrial natriuretic peptide (ANP).
Sodium Regulation
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Ligand-gated Ion Channels01:19

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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.
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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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Covalently Linked Protein Regulators02:04

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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Vibrodissociation of Neurons from Rodent Brain Slices to Study Synaptic Transmission and Image Presynaptic Terminals
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Posttranslational Modification of Sodium Channels.

Zifan Pei1,2, Yanling Pan3, Theodore R Cummins4,5,6

  • 1Department of Biology, Indiana University - Purdue University Indianapolis, Indianapolis, IN, USA.

Handbook of Experimental Pharmacology
|October 27, 2017
PubMed
Summary

Voltage-gated sodium channels (VGSCs) are crucial for cell excitability. This review explores the complex posttranslational modifications impacting VGSC function and cellular physiology.

Keywords:
NavNitrosylationPalmitoylationPhosphorylation

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Physiology

Background:

  • Voltage-gated sodium channels (VGSCs) are key regulators of cellular excitability in neurons and muscle.
  • Their function is influenced by various posttranslational modifications (PTMs).
  • Understanding these modifications is crucial for comprehending normal and abnormal physiological states.

Purpose of the Study:

  • To review the known posttranslational modifications of VGSCs.
  • To highlight the complexity and breadth of regulatory mechanisms affecting VGSC properties.
  • To discuss the impact of PTMs on cellular excitability.

Main Methods:

  • Literature review of studies on VGSC posttranslational modifications.
  • Analysis of identified PTMs including phosphorylation, ubiquitination, palmitoylation, nitrosylation, glycosylation, and SUMOylation.
  • Examination of isoform-specific and interacting effects of PTMs.

Main Results:

  • Numerous PTMs covalently modify VGSCs in neurons and muscle.
  • PTMs profoundly impact cellular excitability, contributing to both normal and pathological conditions.
  • Some modifications affect all VGSC isoforms, while others are isoform-specific.

Conclusions:

  • The modulation of VGSCs by PTMs is complex and still under active investigation.
  • Interactions between different PTMs on VGSCs are not fully understood.
  • Further research is needed to elucidate the full spectrum of VGSC regulation by PTMs.