J. Ramirezlatorre et al., FUNCTIONAL CONTRIBUTIONS OF ALPHA-5 SUBUNIT TO NEURONAL ACETYLCHOLINE-RECEPTOR CHANNELS, Nature, 380(6572), 1996, pp. 347-351
LIGAND-GATED ion channels are multi-subunit complexes where each subun
it-type is encoded by several related genes. Heterologous expression o
f any one of the neuronal nicotinic acetylcholine receptors (nAChR) al
pha-type subunits, either alone or with any beta-type subunit, typical
ly yields functional nAChR channels(1-5). A striking exception is the
nAChR alpha 5 subunit: although apparently complexed with beta 2 and b
eta 4 nAChR subunits in neurons(6-8), and expressed in a subset of neu
rons within the central and peripheral nervous systems(9,10), heterolo
gous expression of alpha 5, either alone or with any beta-type subunit
has failed to yield functional channels(1.11). We demonstrate here th
at alpha 5 does participate in nAChRs expressed in heterologous system
s and in primary neurons, and further that alpha 5 contributes to the
lining of functionally unique nAChR channels, but only if coexpressed
with both another alpha- and beta-type subunit. Furthermore, channels
containing the alpha 5 subunit are potently activated and desensitized
by nanomolar concentrations of nicotine.