Receptors with opposing functions are in postsynaptic microdomains under one presynaptic terminal.
Fast excitatory synaptic transmission through vertebrate autonomic ganglia is mediated by postsynaptic nicotinic acetylcholine receptors (nAChRs). We demonstrate a unique postsynaptic receptor microheterogeneity on chick parasympathetic ciliary ganglion neurons-under one presynaptic terminal, nAChRs and glycine receptors formed separate but proximal clusters. Terminals were loaded with [3H]glycine via the glycine transporter-1 (GlyT-1), which localized to the cholinergic presynaptic terminal membrane; depolarization evoked [3H]glycine release that was calcium independent and blocked by the GlyT-1 inhibitor sarcosine. Ganglionic synaptic transmission mediated by nAChRs was attenuated by glycine. Coexistence of separate clusters of receptors with opposing functions under one terminal contradicts Dale's principle and provides a new mechanism for modulating synaptic activity in vivo.
Tsen
G
G
Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Ave., Boston, Massachusetts 02111, USA.
Williams
B
B
Allaire
P
P
Zhou
Y D
YD
Ikonomov
O
O
Kondova
I
I
Jacob
M H
MH
D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D002829:Choroid / Q000294:innervation / Q000648:ultrastructure; D005726:Ganglia, Parasympathetic / Q000166:cytology; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology; D050487:Glycine Plasma Membrane Transport Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018009:Receptors, Glycine / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012521:Sarcosine / Q000494:pharmacology; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D050487:Glycine Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D018009:Receptors, Glycine; D011978:Receptors, Nicotinic; C073441:gephyrin; D005998:Glycine; D012521:Sarcosine