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nicotinic receptor (nicotinic acetylcholine receptor, nAChR)

Function: - ionotropic nicotinic receptors mediate postsynaptic excitatory responses at the neuromuscular junction - nicotinic receptors may also act presynaptically to modulate acetylcholine release in the periphery - simultaneous binding of 2 molecules of acetylcholine is required for opening of the ion channel - a conformational change that affects all subunits results in opening of the ion channel, permeable primarily to Na+ & secondarily Ca+2 - within the brain, nicotinic receptors function as ligand-gated ion channels linked to rapidly desensitizing Ca2+ influx, with variable permeability of Na+ relative to Ca+2 - role in modulation of release of several neurotransmitters (glutamate, GABA & dopamine), mediating &/or modulating synaptic transmission & plasticity [4] - nicotinic receptors are inhibited by neuromuscular blocking agents. Structure: - skeletal muscle receptors consist of pentamers of (alpha)2-beta-gamma-delta - in mature muscle endplates, the gamma subunit is replaced by an epsilon subunit, (alpha)2-beta-delta-epsilon - in the mammalian CNS, nine different alpha subunits (2-10) & three different beta subunits (2-4) have been described - it is assumed that most receptors are heteropentameric structures, with various combinations of alpha & beta subunits, but some receptors may form as homopentamers, notably alpha-7 (CHRNA7) - these alpha-7 homopentamers along with those containing alpha-4 & beta-2 subunits are the most abundant in brain. Compartment: - cell junction, synapse, - postsynaptic cell membrane, presynaptic cell membrane Expression: - skeletal muscle, specifically at motor endplate - within the brain, present on neurons & on glia. Pathology: - role in neurodegeneration is suggested [4]

Interactions

molecular events

Related

acetylcholine (Miochol, Pragmoline) acetylcholine (nicotinic) receptor antibody CNS cholinergic system myasthenia gravis

Specific

nicotinic receptor alpha4-beta2

General

cholinergic receptor ionotropic receptor multisubunit protein Na+ channel phosphoprotein

Properties

SIZE: MW = 225 kD COMPARTMENT: synaptic membrane CELL: neuron MOTIF: ligand-binding site allosteric site ION-PERMEABILITY: Na+ K+ Ca+2 SUBUNITS: nicotinic receptor alpha (2) MOTIF: exoplasmic domain {N-TERMINAL} glycosylation site transmembrane domain {TM1} transmembrane domain {TM2} transmembrane domain {TM3} transmembrane domain {TM4} exoplasmic domain {C-TERMINAL} cytoplasmic domain {C-TERMINAL} MOTIF: hydrophobic region nicotinic receptor beta subunit MOTIF: exoplasmic domain {N-TERMINAL} MOTIF: cysteine residue {N_TERMINAL} MODIFICATION: cysteine residue {N_TERMINAL} cysteine residue {N_TERMINAL} MODIFICATION: cysteine residue {N_TERMINAL} N-glycosylation site ligand-binding site transmembrane domain {TM1} cytoplasmic loop LOOP#: 1 transmembrane domain {TM2} exoplasmic loop transmembrane domain {TM3} cytoplasmic loop MOTIF: Tyr phosphorylation site LOOP#: 2 transmembrane domain {TM4} exoplasmic domain {C-TERMINAL} nicotinic receptor epsilon MOTIF: exoplasmic domain {1-239} MOTIF: signal sequence {1-20} N-glycosylation site {N86} cysteine residue {C148} MODIFICATION: cysteine residue {C162} N-glycosylation site {N161} cysteine residue {C162} MODIFICATION: cysteine residue {C148} transmembrane domain {240-264} cytoplasmic loop {265-272} transmembrane domain {273-291} exoplasmic loop {292-306} transmembrane domain {307-328} cytoplasmic loop {329-456} transmembrane domain {457-480} exoplasmic domain {481-493} nicotinic receptor delta MOTIF: exoplasmic domain {22-245} MOTIF: signal sequence {1-21} N-glycosylation site {N97} cysteine residue {C151} MODIFICATION: cysteine residue {C165} N-glycosylation site {N164} cysteine residue {C165} MODIFICATION: cysteine residue {C151} transmembrane domain {246-270} cytoplasmic loop {271-277} transmembrane domain {278-299} exoplasmic loop {300-311} transmembrane domain {312-333} cytoplasmic loop {334-471} MOTIF: Tyr phosphorylation site {Y390} transmembrane domain {472-490} exoplasmic domain {491-517} MISC-INFO: LIGAND = NICOTINE MEMBRANE-SPANNING-REGIONS :QUANTITY 4 CONDUCTANCE 25 PS

References

  1. Armstrong TINS 12(3) 117 1989
  2. Kullberg et al Proc Natl Acad Sci U S A 1990 Mar;87(6):2067-71
  3. Barnard EA. Receptor classes and the transmitter-gated ion channels. Trends Biochem Sci. 1992 Oct;17(10):368-74. Review. PMID: 1360717
  4. Fabian-Fine R, Skehel P, Errington ML, Davies HA, Sher E, Stewart MG, Fine A. Ultrastructural distribution of the alpha7 nicotinic acetylcholine receptor subunit in rat hippocampus. J Neurosci. 2001 Oct 15;21(20):7993-8003. PMID: 11588172
  5. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996 pg 178

Components

nicotinic receptor alpha nicotinic receptor beta subunit nicotinic receptor delta; acetylcholine receptor subunit delta (CHRND, ACHRD) nicotinic receptor epsilon; acetylcholine receptor subunit epsilon (CHRNE, ACHRE) nicotinic receptor gamma; acetylcholine receptor subunit gamma (CHRNG, ACHRG)