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Activation

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Voltage Gated Ion Channels

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Voltage-gated ion channel. When the membrane is polarized, the voltage sensing domain of the channel shifts, opening the channel to ion flow (ions represented by yellow circles).

Voltage-gated ion channels react to the voltage differential across the membrane. Portions of the channel domain act as voltage sensors. As the membrane is depolarized, the change in electrostatic forces moves these voltage sensing domains, thus changing the conformation of the channel and opening the pore.[1]

Ligand Gated Ion Channels

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Ligand-gated ion channels react to the binding of ligands. When a ligand is not present, the channel remains in its resting, closed conformation. When the ligand is present, the ligand will bind to an extracellular receptor on or near the channel, which results in a conformational change in the channel, opening the pore to ion permeation.[2]

Inactivation

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Inactivation occurs while the channel remains open. A second gate may close on the channel blocking ion permeation, whilst the channel is still in its open state.

Ball and Chain Inactivation

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Voltage gated ion channel in its closed, open, and inactivated states. Note the channel is still in its open state, but the ball domain blocks ion permeation, therefore the channel is inactivated.

The ball and chain model, also known as N-type inactivation or hinged lid inactivation, is a gating mechanism for some voltage-gated ion channels. Voltage-gated ion channels are composed of four α subunits, one or more of which will have a ball domain located on its cytoplasmic N-terminus. The ball domain is electrostatically attracted to the inner channel domain. When the ion channel is activated, the inner channel domain is exposed, and within milliseconds the chain will fold and the ball will enter the channel, occluding ion permeation. The channel returns to its closed state, blocking the channel domain, and the ball leaves the pore.

Deactivation

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As the membrane depolarizes, the voltage differential is not sufficient to keep the channel in its open state, causing the channel to closes.

Deactivation is the closing of the ion channel. For voltage gated channels this occurs after the voltage differential the originally caused the channel to open is lost.[1] For ligand gated channels this occurs when the ligand dissociates from the channel's receptor.

Potential Sources

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"A hydrophobic gate in an ion channel: the closed state of the nicotinic acetylcholine receptor."

https://www.ncbi.nlm.nih.gov/pubmed/?term=A+hydrophobic+gate+in+an+ion+channel%3A+the+closed+state+of+the+nicotinic+acetylcholine+receptor

"Point mutations affecting antagonist affinity and agonist dependent gating of GABAA receptor channels"

https://www.ncbi.nlm.nih.gov/pubmed/1376242?dopt=Abstract&holding=npg

"Structure and gating mechanism of the acetylcholine receptor pore"

https://www.nature.com/articles/nature01748

"Coupling of agonist binding to channel gating in the GABAA receptor"

https://www.ncbi.nlm.nih.gov/pubmed/12529644?dopt=Abstract&holding=npg

  1. ^ a b Bähring, Robert; Covarrubias, Manuel (2011-01-28). "Mechanisms of closed-state inactivation in voltage-gated ion channels". The Journal of Physiology. 589 (3): 461–479. doi:10.1113/jphysiol.2010.191965. ISSN 0022-3751. PMC 3055536. PMID 21098008.
  2. ^ "Gene group | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2018-11-22.