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Functional contribution of the α7 subunit to multiple subtypes of nicotinic receptors in embryonic chick sympathetic neurones
Author(s) -
Yu C. Ron,
Role Lorna W.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.651bm.x
Subject(s) - homomeric , methyllycaconitine , protein subunit , acetylcholine receptor , nicotinic agonist , microbiology and biotechnology , chemistry , nicotinic acetylcholine receptor , biophysics , receptor , biology , neuroscience , biochemistry , gene
1 Many studies of the α7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) family have demonstrated that this α‐bungarotoxin (α‐BgTx)‐binding neuronal receptor can participate in ACh‐gated channels. Heterologous expression studies reveal that α7 subunits form homomeric channels of unusually high Ca 2+ permeability. However, the physiological role of the α7 subunit in native neuronal nAChR channels is less clear. 2 We present evidence that the α7 subunit contributes to the function of at least three subtypes of native nAChR expressed by embryonic chick sympathetic neurones. These subtypes are functionally distinct from heterologously expressed homomeric α7 nAChRs as well as homomeric‐like currents described in studies of hippocampal and parasympathetic neurones. 3 The proposed nAChRs differ from one another and from homomeric α7 nAChRs in their sensitivity to block by α7 subunit‐specific antagonists: α‐BgTx and methyllycaconitine (MLA). While MLA blocks 60 % of the macroscopic ACh response, α‐BgTx inhibits a small component of the macroscopic current described by slow‐on and slow‐off kinetics. 4 Functional deletion of the α7 subunit by antisense oligonucleotide treatment eliminates the susceptibility of the nAChRs to block by both MLA and α‐BgTx. 5 Single channel recordings combined with pharmacological and antisense‐mediated ‘deletion’ techniques reveal that α‐BgTx‐sensitive α7‐containing nAChRs have a small unitary conductance (18 pS), brief open time kinetics and relatively low open probability ( P o ). MLA‐sensitive α7 nAChRs are characterized by a conductance of ≈35 pS, intermediate burst duration, and a relatively high P o . 6 The third nAChR subtype deleted by α7 antisense treatment is characterized by a unitary conductance of 50 pS and prolonged opening duration. 7 We propose that these three populations of native α7‐containing nAChRs are distinct heteromeric complexes that include other α and/or β nAChR subunits.