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Date
10/10/2011 18:35:27
Group number
PI name
Rodríguez, A.
Channel family
Nicotinic acetylcholine receptor (nAChR)
Channel name
alpha9alpha10 nAChRs
Channel subunit
alpha9, alpha10
UNIPROT
Relevant publication (1)
Elgoyhen et al. Alpha 9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. Cell (1994) 79:705-715
Relevant publication (2)
Elgoyhen et al. Alpha10: a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells. Proc. Natl. Acad. Sci. U.S.A. (2001) 98:3501-3506
Relevant publication (3)
Sgard et al. A novel human nicotinic receptor subunit, alpha10, that confers functionality to the alpha9-subunit. Mol. Pharmacol. (2002) 61:150- 159.
CD
FTIR
NMR
Absorbance /
Fluorescence
Interaction protein (1)
small-conductance Ca(2+)-activated K+ channel type 2 (SK2 channel; Nie et al. Cloning and expression of a small-conductance Ca(2+)-activated K+ channel from the mouse cochlea: coexpression with alpha9/alpha10 acetylcholine receptors. J Neurophysiol. (2004) 91: 1536-1544.
Interaction protein (2)
Interaction protein (3)
Interaction protein (4)
PDB (1)
PDB (2)
PDB (3)
Expression tissues
Restricted expression.
Alpha9 and/or alpha10 nAChRs subunits have been detected in in the nasal epithelium, in the outer hair cells of the cochlea, in the pars tuberalis of the hypophysis, and in the developing muscle of the tongue.

Also expressed in the neurons of dorsal root ganglia and in chromaffin cells from the rat adrenal medulla
(Elgoyhen et al. Alpha 9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells. Cell (1994) 79:705-715; Lips et al. Coexpression of alpha 9 and alpha 10 nicotinic acetylcholine receptors in rat dorsal root ganglion neuron. Neuroscience (2002) 115:1-5; Colomer at al. Functional characterization of alpha9-containing cholinergic nicotinic receptors in the rat adrenal medulla: implication in stress-induced functional plasticity. J Neurosci. (2010) 30: 6732-6742)
Expression cell lines
Expression plasmids
Level of expression
Channel quaternary
Pentamer (3 alpha9, 2 alpha10)
Agonists
Acetylcholine, choline, oxotremorine-M
(Elgoyhen et al. Alpha10: a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells. Proc. Natl. Acad. Sci. U.S.A. (2001) 98:3501-3506; Baker at al. Pharmacological properties of alpha 9 alpha 10 nicotinic acetylcholine receptors revealed by heterologous expression of subunit chimeras. Mol. Pharmacol. (2004) 65:453-460)
Smile agonist
Antagonists and blockers
Nicotine
atropine
strychnine
methyllycaconitine
alpha-bungarotoxin
alpha-conotoxin RgIA
(Elgoyhen et al. Alpha10: a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells. Proc. Natl. Acad. Sci. U.S.A. (2001) 98:3501-3506; Baker at al. Pharmacological properties of alpha 9 alpha 10 nicotinic acetylcholine receptors revealed by heterologous expression of subunit chimeras. Mol. Pharmacol. (2004) 65:453-460; Ellison et al. Alpha-RgIA: a novel conotoxin that specifically and potently blocks the alpha9alpha10 nAChR. Biochemistry (2006) 45: 1511-1517)
Smile antagonist
Structure-function
relationship
Molecular determinant assembly
Molecular determinant clustering
Molecular determinant trafficking
Molecular determinant binding
Arg112 in the complementary alpha10 (-) subunit is a determinant fro recognition in the site that binds small ligands.
Glu195 in the principal alpha(+), and Asp114 in the complementary alpha10(-) subunit might confer the potency and selectivity to alpha-conotoxin RgIA when interacting with Arg7 and Arg9 of this ligand (Pérez et al. Molecular modeling of the alpha9alpha10 nicotinic acetylcholine receptor subtype. Bioorg. Med. Chem Lett. (2008), doi:10.1016/j.bmcl.2008.10.094).

Mutants constructs
Antibodies
Anti-alpha9 (E17; sc-13806) and anti-alpha10 (N-18; sc-18277) from Santa Cruz Biotech, Inc (CA, USA).
Diseases
In humans, alpha9 nicotinic acetylcholine receptor is coupled to physiological regulation of keratinocyte adhesion, and its interaction with Pemphigus vulgaris autoantibodies may lead to blister development (Nguyen et al. Novel human alpha9 acetylcholine receptor regulating keratinocyte adhesion is targeted by Pemphigus vulgaris autoimmunity. Am. J. Pathol. (2000) 157:1377-1391).

 

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