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Voltage-gated sodium channels (VGSCs), also known as voltage-dependent sodium channels (VDSCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the sodium ion Na +. They are the main channels involved in action potential of excitable cells.
When the membrane's voltage becomes low enough, the inactivation gate reopens and the activation gate closes in a process called deinactivation. With the activation gate closed and the inactivation gate open, the Na + channel is once again in its deactivated state, and is ready to participate in another action potential.
In sodium channels, inactivation appears to be the result of the actions of helices III-VI, with III and IV acting as a sort of hinged lid that block the channel. The exact mechanism is poorly understood, but seems to rely on a particle that has a high affinity for the exposed inside of the open channel. [ 26 ]
Persistent sodium current generation is hypothesized to occur by the incomplete inactivation of the voltage-gated sodium channel current (INa), where the channel becomes constitutively active and conducts sodium, creating a "persistently active" inward sodium current. Upon depolarization, the four identical motifs of the sodium channel (which ...
where ¯ + is the maximum sodium conductance, m is the activation gate, and h is the inactivation gate (both gates are shown in the adjacent image). [4] The values of m and h vary between 0 and 1, depending upon the transmembrane potential. Transmembrane voltage response of a space-clamped mammalian node of Ranvier
Mutations altering the usual structure and function of this sodium channel therefore disrupt regulation of muscle contraction, leading to episodes of severe muscle weakness or paralysis. Mutations have been identified in residues between transmembrane domains III and IV which make up the fast inactivation gate of Na v 1.4. Mutations have been ...
Ball and chain inactivation can only happen if the channel is open. In neuroscience, ball and chain inactivation is a model to explain the fast inactivation mechanism of voltage-gated ion channels. The process is also called hinged-lid inactivation or N-type inactivation. A voltage-gated ion channel can be in three states: open, closed, or ...
Similarly, the probability of the voltage-sensitive sodium channel was modeled to have three similar gates of probability m and a fourth gate, associated with inactivation, of probability h; thus, p open, Na = m 3 h. The probabilities for each gate are assumed to obey first-order kinetics
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