The rescue of developing avian motoneurons from programmed cell death by a selective inhibitor of the fetal muscle-specific nicotinic acetylcholine receptor.
In an attempt to determine whether the rescue of developing motoneurons (MNS) from programmed cell death (PCD) in the chick embryo following reductions in neuromuscular function involves muscle or neuronal nicotinic acetylcholine receptors (nAChRs), we have employed a novel cone snail toxin alphaA-OIVA that acts selectively to antagonize the embryonic/fetal form of muscle nAChRs. The results demonstrate that alphaA-OIVA is nearly as effective as curare or alpha-bungarotoxin (alpha-BTX) in reducing neuromuscular function and is equally effective in increasing MN survival and intramuscular axon branching. Together with previous reports, we also provide evidence consistent with a transition between the embryonic/fetal form to the adult form of muscle nAChRs in chicken that involves the loss of the gamma subunit in the adult receptor. We conclude that selective inhibition of the embryonic/fetal form of the chicken muscle nAChR is sufficient to rescue MNs from PCD without any involvement of neuronal nAChRs.
Oppenheim
Ronald W
RW
Department of Neurobiology and Anatomy and The Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. roppenhm@wfubmc.edu
Calderó
Jordi
J
Cuitat
Doloros
D
Esquerda
Josep
J
McArdle
Joseph J
JJ
Olivera
Baldomero M
BM
Prevette
David
D
Teichert
Russell W
RW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002038:Bungarotoxins / Q000494:pharmacology; D002470:Cell Survival; D002642:Chick Embryo; D020916:Conotoxins / Q000494:pharmacology; D003472:Curare / Q000494:pharmacology; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009068:Movement / Q000187:drug effects; D009469:Neuromuscular Junction / Q000166:cytology* / Q000187:drug effects / Q000196:embryology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism
D002038:Bungarotoxins; D020916:Conotoxins; D018733:Nicotinic Antagonists; D010456:Peptides, Cyclic; D011978:Receptors, Nicotinic; D014404:Tubulin; C492637:alphaA-conotoxin OIVA; D003472:Curare