A neuronal nicotinic acetylcholine receptor subunit (α7) is developmentally regulated and forms a homo-oligomeric channel blocked by α-BTX

Abstract

cDNA and genomic clones encoding alpha 7, a novel neuronal nicotinic acetylcholine receptor (nAChR) alpha subunit, were isolated and sequenced. The mature alpha 7 protein (479 residues) has moderate homology with all other alpha and non-alpha nAChR subunits and probably assumes the same transmembrane topology. alpha 7 transcripts transiently accumulate in the developing optic tectum between E5 and E16. They are present in both the deep and the superficial layers of E12 tectum. In Xenopus oocytes, the alpha 7 protein assembles into a homo-oligomeric channel responding to acetylcholine and nicotine. The alpha 7 channel desensitizes very rapidly, rectifies strongly above -20 mV, and is blocked by alpha-bungarotoxin. A bacterial fusion protein encompassing residues 124-239 of alpha 7 binds labeled alpha-bungarotoxin. We conclude that alpha-bungarotoxin binding proteins in the vertebrate nervous system can function as nAChRs.

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

“…A different possibility for the lack of rapid desensitization is that presynaptic ␣7-nAChRs may differ in composition from the homomeric ␣7-nAChR described previously (Couturier et al, 1990;Schoepfer et al, 1990;Chen and Patrick, 1997;Drisdel and Green, 2000). Heteromeric receptors containing the ␣7 and ␤2 gene products can be produced by heterologous coexpression, and the receptors have diminished rates of desensitization (Khiroug et al, 2002).…”

“…This regulation is made possible by the fact that all vertebrate nAChRs, including both muscle and neuronal receptors, are cation-selective ligand-gated ion channels with significant relative permeabilities to calcium. The most extreme appears to be that of nicotinic receptors containing the ␣7 gene product (Couturier et al, 1990;Schoepfer et al, 1990); they equal or exceed NMDA receptors in relative calcium permeability (Bertrand et al, 1993;Seguela et al, 1993). Such receptors (␣7-nAChRs) are one of the two most abundant nicotinic receptor subtypes expressed in brain (Sargent, 1993;Gotti et al, 1994;Lindstrom, 1996;Role and Berg, 1996;Conroy and Berg, 1998), and in contrast to NMDA receptors, they do not require the postsynaptic membrane to be depolarized before promoting calcium influx.…”

Functional significance of aromatic amino acids from three peptide loops of the α7 neuronal nicotinic receptor site investigated by site‐directed mutagenesis

“…The 1057 bp t~ll ('bit -153)-~/!1 6NT 90~) and the 2122 bp B£I !1 (NT 904)-~coRi (NT 3026) flra41m~ts fgom plasmid flip -'7 delta [13]. wore Ill,rod and suh¢lon~:l I~.tw~…”

Postnatal expression of α2 nicotinic acetylcholine receptor subunit mRNA in developing cortex and hippocampus

“…In the rat, a total of eight ligand binding α and three structural β subunits have been cloned, which in various combinations of α and β subunits, form distinct heteromeric or homomeric pentameric receptor subtypes (Couturier et al, 1990;Seguela et al, 1993, Sargent, 1993, Corringer et al, 2000. After cloning and characterization of the muscle type nAChR subunits (α1, β1, δ ,ε, γ ), the α2 was the first neuronal subunit to be cloned, sequenced and characterized (α2, Wada et al, 1988) followed by α3 (Boulter et al, 1986), α4 (Goldman et al, 1987), β2 , β3 , β4 (Isenberg andMeyer, 1989, Duvoisin et al, 1989), α5 (Boulter et al, 1990), α6, (Lamar et al, 1990), α7 (Seguela et al, 1993), α9 (Elgoyhen et al, 1994) and finally α 10 (Elgoyhen et al, 2001).…”