Functional contribution of the alpha5 subunit to neuronal nicotinic channels expressed by chick sympathetic ganglion neurones

J Physiol. 1998 Jun 15;509 ( Pt 3)(Pt 3):667-81. doi: 10.1111/j.1469-7793.1998.667bm.x.


1. Heterologous expression studies of the alpha5 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 alpha- and a beta-subunit. Previous studies also indicate prominent expression of alpha5 in both central and peripheral nervous systems. The participation of alpha5 in native nAChRs and its functional role in these channels is, however, unknown. 2. In this study, we present evidence that alpha5 has a role in at least two distinct subtypes of nAChR complexes expressed by embryonic chick sympathetic neurones. 3. alpha5 contributes not only to agonist but also to antagonist sensitivity of natively expressed nAChR channels. Functional deletion of the alpha5 subunit by antisense oligonucleotide treatment removes the nAChRs with relatively low affinity to ACh and cytisine. Deletion of alpha5 also eliminates channels that are blocked by the alpha7-specific antagonist methyllycaconitine (MLA) while increasing the percentage of current carried by nAChRs that are sensitive to alpha-bungarotoxin (alpha-BgTx). 4. Single channel analyses indicate that functional deletion of alpha5 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, alpha-BgTx-sensitive native nAChRs normally detected in sympathetic neurones at later developmental stages. 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 sympathetic neurones throughout development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / pharmacology
  • Aconitine / analogs & derivatives
  • Aconitine / pharmacology
  • Alkaloids / pharmacology
  • Animals
  • Antisense Elements (Genetics)
  • Azocines
  • Bungarotoxins / pharmacology
  • Chick Embryo
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Ganglia, Sympathetic / cytology
  • Gene Deletion
  • Insecticides / pharmacology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Mutagenesis / physiology
  • Neurons / chemistry*
  • Neurons / physiology
  • Nicotinic Agonists / pharmacology
  • Nicotinic Antagonists / pharmacology
  • Quinolizines
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / genetics*
  • Receptors, Nicotinic / metabolism*


  • Alkaloids
  • Antisense Elements (Genetics)
  • Azocines
  • Bungarotoxins
  • Insecticides
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Quinolizines
  • Receptors, Nicotinic
  • methyllycaconitine
  • cytisine
  • Acetylcholine
  • Aconitine