Ball and chain inactivation

Diagram of a voltage-gated ion channel in the open, closed and inactivated state
Diagram of a voltage-gated ion channel, showing the three states: closed, open, and inactivated. 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 inactivated. The inactivated state is mainly achieved through fast inactivation, by which a channel transitions rapidly from an open to an inactivated state. The model proposes that the inactivated state, which is stable and non-conducting, is caused by the physical blockage of the pore. The blockage is caused by a "ball" of amino acids connected to the main protein by a string of residues on the cytoplasmic side of the membrane. The ball enters the open channel and binds to the hydrophobic inner vestibule within the channel. This blockage causes inactivation of the channel by stopping the flow of ions.[1][2] This phenomenon has mainly been studied in potassium channels and sodium channels.[3]

  1. ^ Nicholls JG, Martin AR, Wallace BG, Fuchs PA (2011). From neuron to brain (8th ed.). Sunderland, Mas.: Sinauer Associates. pp. 123–124. ISBN 978-0878936090.
  2. ^ Brady S, Siegel G, Albers RW, Price D (2012). Basic neurochemistry: molecular, cellular and medical aspects (8th ed.). Amsterdam; London: Academic Press. pp. 106–107. ISBN 978-0080959016.
  3. ^ Aldrich RW (2001). "Fifty years of inactivation". Nature. 411 (6838). Nature Publishing Group: 643–644. Bibcode:2001Natur.411..643A. doi:10.1038/35079705. PMID 11395746. S2CID 4373704.