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Voltage-gated sodium channels in neurological disorders
Mohamed Chahine1, Aurélien Chatelier, Olga Babich
1Le Centre de recherches Université Laval Robert-Griffard, Quebec City, Guebec, Canada.
CNS & Neurological Disorders Drug Targets
|June 10, 2008
Summary
Voltage-gated sodium channels (VGSCs) are crucial for electrical signaling in neurons. This review details their properties and roles in neurological disorders, highlighting implications of channel dysfunction.
Area of Science:
- Neuroscience
- Biophysics
- Pharmacology
Background:
- Voltage-gated sodium channels (VGSCs) are critical for electrical signal transmission in excitable cells, including neurons.
- These channels are composed of alpha and beta subunits and are essential for action potential (AP) generation and propagation in the peripheral (PNS) and central nervous systems (CNS).
Purpose of the Study:
- To review the biochemical, biophysical, and pharmacological properties of neuronal VGSCs.
- To explore the implications of VGSC dysfunction in various neurological disorders.
Main Methods:
- Literature review of existing research on neuronal VGSCs.
- Analysis of studies linking VGSC mutations, expression changes, and modulation to cellular electrical instability and pathological conditions.
Main Results:
- Mutations, altered expression, or improper modulation of VGSCs can cause membrane electrical instability and spontaneous activity.
- Dysfunctional VGSCs are implicated in the pathophysiology of several neurological diseases.
Conclusions:
- Neuronal VGSCs are key players in normal and pathological neurological function.
- Understanding VGSC properties is vital for developing therapeutic strategies for neurological disorders.
Related Concept Videos
01:26Voltage-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 types of...
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...
01:26Voltage-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 types of...
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...
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.
01:19The Role of Ion Channels in Neuronal Computation
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.
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...