Functional contribution of the α5 subunit to neuronal nicotinic channels expressed by chick sympathetic ganglion neurones

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Abstract
Heterologous expression studies of the α5 subunit of the neuronal acetylcholine receptor (nAChR) gene family have demonstrated that it can participate in the function of ACh‐gated channels if co‐expressed with another α‐ and a β‐subunit. Previous studies also indicate prominent expression of α5 in both central and peripheral nervous systems. The participation of α5 in native nAChRs and its functional role in these channels is, however, unknown. In this study, we present evidence that α5 has a role in at least two distinct subtypes of nAChR complexes expressed by embryonic chick sympathetic neurones. α5 contributes not only to agonist but also to antagonist sensitivity of natively expressed nAChR channels. Functional deletion of the α5 subunit by antisense oligonucleotide treatment removes the nAChRs with relatively low affinity to ACh and cytisine. Deletion of α5 also eliminates channels that are blocked by the α7‐specific antagonist methyllycaconitine (MLA) while increasing the percentage of current carried by nAChRs that are sensitive to α‐bungarotoxin (α‐BgTx). Single channel analyses indicate that functional deletion of α5 results in the deletion of both the ‘brief’ and ‘long’ open duration, 50 pS subtypes of nAChR channels while increasing the expression of the 18 pS, α‐BgTx‐sensitive native nAChRs normally detected in sympathetic neurones at later developmental stages. 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 sympathetic neurones throughout development.