Glycine receptor

Source: Wikipedia, the free encyclopedia.
Glycine

The glycine receptor (abbreviated as GlyR or GLR) is the

ionotropic receptor that produces its effects through chloride currents. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brainstem.[1]

The receptor can be activated by a range of simple

β-alanine and taurine, and can be selectively blocked by the high-affinity competitive antagonist strychnine.[2] Caffeine is a competitive antagonist of GlyR.[3] Cannabinoids enhance the function.[4]

The protein

neurons despite the presence of GABAA receptors.[7]

History

Glycine and its receptor were first suggested to play a role in inhibition of cells in 1965.[8] Two years later, experiments showed that glycine had a hyperpolarizing effect on spinal motor neurons[9] due to increased chloride conductance through the receptor.[10] Then, in 1971, glycine was found to be localized in the spinal cord using autoradiography.[11] All of these discoveries resulted in the conclusion that glycine is a primary inhibitory neurotransmitter of the spinal cord that works via its receptor.

Arrangement of subunits

(a): shows three agonists and one antagonist of the glycine receptor. (b): the fetal form of the receptor is made up of five α2 subunits, while the adult form is made up of both α1 and β subunits.

Strychnine-sensitive GlyRs are members of a family of

cell lines, which are useful for studies of channel pharmacokinetics and pharmacodynamics.[14] The β subunit is unable to form functional channels without α subunits but determines the synaptic localization of GlyRs and the pharmacological profile of glycinergic currents.[16]

Function

Adults

In mature adults, glycine is a inhibitory neurotransmitter found in the spinal cord and regions of the brain.[15] As it binds to a glycine receptor, a conformational change is induced, and the channel created by the receptor opens.[17] As the channel opens, chloride ions are able to flow into the cell which results in hyperpolarization. In addition to this hyperpolarization, which decreases the likelihood of action potential propagation, glycine is also responsible for decreasing the release of both inhibitory and excitatory neurotransmitters as it binds to its receptor.[18] This is called the "shunting" effect and can be explained by Ohm's Law. As the receptor is activated, the membrane conductance is increased and the membrane resistance is decreased. According to Ohm's Law, as resistance decreases, so does voltage. A decreased postsynaptic voltage results in a decreased release of neurotransmitters.[18]

Embryos

In developing embryos, glycine has the opposite effect as it does in adults. It is an excitatory neurotransmitter.

NKCC1. This moves one sodium, one potassium and two chloride ions into the cell, resulting in a higher intracellular chloride concentration. When glycine binds to its receptor, the result is an efflux of chloride, instead of an influx as it happens in mature adults. The efflux of chloride causes the membrane potential to become more positive, or depolarized. As the cells mature, the K+-Cl- cotransporter 2 (KCC2) is expressed, which moves potassium and chloride out of the cell, decreasing the intracellular chloride concentration. This allows the receptor to switch to an inhibitory mechanism as described above for adults.[18]

Glycine receptors in diseases

Disruption of GlyR surface expression or reduced ability of expressed GlyRs to conduct chloride ions results in the rare neurological disorder,

stiff person syndrome.[19]

Ligands

Agonists

Positive Allosteric Modulators

Antagonists

References

  1. ^
    PMID 15383648
    .
  2. PMID 9131721
    .
  3. PMID 19564396
    .
  4. PMID 21460829
    .
  5. ^
    PMID 14715953
    .
  6. PMID 9812897
    .
  7. PMID 24920633
    .
  8. PMID 5866625
    .
  9. S2CID 4198837
    .
  10. PMID 4384497
    .
  11. PMID 4329648
    .
  12. S2CID 205209809
    .
  13. S2CID 25411536
    .
  14. ^
    S2CID 42056647
    .
  15. ^
    PMID 9131721
    .
  16. PMID 26255765
    .
  17. S2CID 41022948
    .
  18. ^
    S2CID 247871
    .
  19. ^ Online Mendelian Inheritance in Man (OMIM): STIFF-PERSON SYNDROME; SPS - 184850
  20. PMID 11278873
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Glycine_receptor&oldid=1211845236"