Cr. Yu et Lw. Role, FUNCTIONAL CONTRIBUTION OF THE ALPHA-7 SUBUNIT TO MULTIPLE SUBTYPES OF NICOTINIC RECEPTORS IN EMBRYONIC CHICK SYMPATHETIC NEURONS, Journal of physiology, 509(3), 1998, pp. 651-665
1. Madly studies of the alpha 7 subunit of the neuronal nicotinic acet
ylcholine receptor (nAChR) family have demonstrated that this cc-bunga
rotoxin (alpha-BgTx)-binding neuronal receptor can participate in ACh-
gated channels. Heterologous expression studies reveal that alpha 7 su
bunits form homomeric channels of unusually high Ca2+ permeability. Ho
wever, the physiological role of the alpha 7 subunit in native neurona
l nAChR channels is less clear. 2. We present evidence that the alpha
7 subunit contributes to the function of at least three subtypes, of n
ative nAChR expressed by embryonic chick sympathetic neurones. These s
ubtypes functionally distinct from heterologously expressed homomeric
alpha 7 nAChRs as well as homomeric-like currents described in studies
of hippocampal and parasympathetic neurones. 3. The proposed nAChRs d
iffer from one another and from homomeric alpha 7 nAChRs in their sens
itivity to block by alpha 7 subunit-specific antagonists: alpha-BgTx a
nd methyllycaconitine (MLA). While MLA blocks 60% of the macroscopic A
Ch response, alpha-BgTx inhibits a small component of the macroscopic
current described by slow-on and slow-off kinetics. 4. Functional dele
tion of the alpha 7 subunit by antisense oligonucleotide treatment eli
minates the susceptibility of the nAChRs to block by both MLA and alph
a-BgTx. 5. Single channel recordings combined with pharmacological and
antisense-mediated 'deletion' techniques reveal that alpha-BgTx-sensi
tive alpha 7-containing nAChRs have a small unitary conductance (18 pS
), brief open time kinetics and relatively low open probability (P-o).
MLA-sensitive alpha 7 nAChRs are characterized by a conductance of si
milar to 35 pS, intermediate burst duration, and a relatively high P-o
. 6. The third nAChR subtype deleted by alpha 7 antisense treatment is
characterized by a unitary conductance of 50 pS and prolonged opening
duration. 7. We propose that these three populations of native alpha
7-containing nAChRs are distinct heteromeric complexes that include ot
her alpha and/or beta nAChR subunits.