Cr. Yu et Lw. Role, FUNCTIONAL CONTRIBUTION OF THE ALPHA-5 SUBUNIT TO NEURONAL NICOTINIC CHANNELS EXPRESSED BY CHICK SYMPATHETIC-GANGLION NEURONS, Journal of physiology, 509(3), 1998, pp. 667-681
1. Heterologous expression studies of the alpha 5 subunit of the neuro
nal acetylcholine receptor (nAChR) gene family have demonstrated that
it can participate in the function of ACh-gated channels if co-ex-pres
sed with another alpha- and a beta-subunit. Previous studies also indi
cate prominent expression of alpha 5 in both central and peripheral ne
rvous systems. The participation of alpha 5 in native nAChRs and its f
unctional role in these channels is, however, unknown. 2. In this stud
y, we present evidence that alpha 5 has a role in at least two distinc
t subtypes of nAChR complexes expressed by embryonic chick sympathetic
neurones. 3. alpha 5 contributes not only to agonist but also to anta
gonist sensitivity of natively expressed nAChR channels. Functional de
letion of the alpha 5 subunit by antisense oligonucleotide treatment r
emoves the nAChRs with relatively low affinity to ACh and cytisine. De
letion of alpha 5 also eliminates channels that are blocked by the alp
ha 7-specific antagonist methyllycaconitine (MLA) while increasing the
percentage of current carried by nAChRs that are sensitive to alpha-b
ungarotoxin (alpha-BgTx). 4. Single channel analyses indicate that fun
ctional deletion of alpha 5 results in the deletion of both the 'brief
' and 'long' open duration, 50 pS subtypes of nAChR channels while inc
reasing the expression of the 18 pS, alpha-BgTx-sensitive native nAChR
s normally detected in sympathetic neurones at later developmental sta
ges. 5. The biophysical and pharmacological profiles of native nAChRs
revealed by this study and previous work are discussed in the context
of a proposed model of the nAChR channels expressed by chick sympathet
ic neurones throughout development.