Ion-channel-coupled receptor

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The ion-channel-coupled receptors, also called ligand-gated ion channels, are one of the three main cell membrane receptor. They play an important role in the transmission of neuronal signals at the synapses and the neuromuscular junctions (NMJ)[1].

Depending upon which neurotransmitter they bind, these receptors can be classified as excitatory and inhibitory.


Contents

Excitatory receptors

They are cation channels that depolarize the membrane towards the action potential.

Nicotinic Acetylcholine receptor (nAChR)

This cholinergic receptor was the first receptor in history to be indentified and named[2]. It binds the excitatory neurotrasmitter acetylcholine (ACh). They can be found in neurons of the CNS and the ANS ganglia, as well as in the muscle cells at the NMJ[3]. The receptor is composed of five subunits (heteropentamer) and each subunit has 4 transmembrane domians[4].

The receptors at the NMJ are composed of 2α, 1β, 1γ, 1δ subunits, whereas the ones in the ganglia and CNS have 2α, 3β subunits. The α-subunit has the binding-site for ACh.

nAChRs are blocked by the snake venom alpha-bungarotoxin and the poisonous extract curare.


Glutamate receptor

Glutamate is the major excitatory neurotransmitter in the CNS. The glutamate receptors are composed of 4 subunits (tetramers) each one with 3 transmembrane domains and 1 loop segment which inserts into the membrane [5]. These receptors can be classified in three subtypes [6]:

NMDA receptors

Present on all neurons, they are specially permeable to Ca2+ and produce a slow excitatory transmission. They are form from the subunits NR1 and NR2 (A - D). Since this receptor is voltage-block by Mg2+, it requires membrane depolarization to open its channels. Additionally it requires the binding of glycine to an allosteric site.

AMPA receptors

Also present on all neurons, they are permeable to Na+ and K+ but not to Ca2+ and produce a fast excitatory transmission. They are composed of 4 subunits: GluR1 - 4.

KA receptors

Kainate receptors are present mainly in neurons in the hippocampus, cerebellum and spinal cord. They are formed by the subunits GluK1 - 5.


5-HT3 (Serotonin) receptors

From all the subtypes of 5-HT receptors, only the 5-HT3 subtype is an ion channel[7]. It has a similar structure to the nAChR, with 5 subunits each one with 5 TMD.


Inhibitory receptors

GABAA receptors

The GABAA receptors are permeable to Cl- and are present in the CNS. They have similar structure to the nAChR but with a wider variety of constitutive subunits, therefore with more subtypes of receptors. They contain at least one α and one β subunits. The neurotransmitter GABA binds to the β subunit.

Valium is an agonist of this receptor and picrotoxin is an antagonist[8].


Glycine receptors

These receptors, also similar in structure to the nAChR, are Cl- channels and can be found only in the spinal cord and the brain stem. They are formed by 3α and 2β subunits. Strychnine (used in some rat poisons) potently blocks this receptor[9].


References

  1. Alberts, et al. Molecular Biology of the Cell. 5th ed. Garland Science. 2008
  2. Langley, J. N. On the contraction of muscle chiefly in relation to the presence of receptive substances. Part 1. J. Physiol. (Lond.) 36, 347–384 (1907).
  3. Katzung, et al. Basic and Clinical Pharmacology. 11th ed. McGraw Hill. 2009
  4. Unwin N. The nicotinic acetylcholine receptor of the Torpedo electric ray. J Struct Biol. 1998;121(2):181-90.
  5. Seeburg PH. The molecular biology of mammalian glutamate receptor channels. Trends Pharmacol Sci. 1993 Aug;14(8):297-303.
  6. Katzung, et al.
  7. Katzung, et al.
  8. Katzung et al.
  9. Katzung et al.
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