Desensitization_ Desensitised State

A condition in which a receptor is unresponsive despite the presence of agonist; also referred to as a ‘refractory state’. Typically this state is the consequence of prolonged exposure to agonist, and occurs after receptor activation; it is a built in mechanism to limit a receptor’s effects.

Mechanistically the desensitised state differs from the resting, closed state of a receptor because in the latter state, a receptor can respond to agonist. This difference predicts that these states are structurally distinct.

  • The desensitised state may also be stabilised by very low concentrations of agonist, such that no measurable activation of the receptor precedes it.
  • Desensitisation is an intrinsic property of many receptors but can also be influenced by other interactions or modifications, such as phosphorylation.

Desensitization is the rapidly attenuation of receptor activation as a result of stimulation of cells and occurs in seconds to minutes. Receptor phosphorylation by  G-protein-coupled receptor kinases and secondmessenger- regulated kinases as well as receptor/ G-protein uncoupling contribute to this process.

In the continued presence or at high concentrations of agonistic ligands, ligand gated ion channels may undergo desensitization by entering a permanently closed state.While the ligand binding domain is occupied by the agonist, the desensitized channel is unable to re-open. For ligandgated ion channels, the structural basis of desensitization is not understood. For voltage-gated K+ channels, the ‘ball and chain’ model suggests a mechanism of ion channel desensitization.

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