A new Conus peptide ligand for mammalian presynaptic Ca2+ channels.
Voltage-sensitive Ca2+ channels that control neurotransmitter release are blocked by omega-conotoxin (omega-CgTx) GVIA from the marine snail Conus geographus, the most widely used inhibitor of neurotransmitter release. However, many mammalian synapses are omega-CgTx-GVIA insensitive. We describe a new Conus peptide, omega-CgTx-MVIIC, that is an effective inhibitor of omega-CgTx-GVIA-resistant synaptic transmission. Ca2+ channel targets that are inhibited by omega-CgTx-MVIIC but not by omega-CgTx-GVIA include those mediating depolarization-induced 45Ca2+ uptake in rat synaptosome preparations, "P" currents in cerebellar Purkinje cells, and a subset of omega-CgTx-GVIA-resistant currents in CA1 hippocampal pyramidal cells. The characterization of omega-CgTx-MVIIC by a combination of molecular genetics and chemical synthesis defines a general approach for obtaining ligands with novel receptor subtype specificity from Conus.
Hillyard
D R
DR
Department of Biology, University of Utah, Salt Lake City 84132.
Monje
V D
VD
Mintz
I M
IM
Bean
B P
BP
Nadasdi
L
L
Ramachandran
J
J
Miljanich
G
G
Azimi-Zoonooz
A
A
McIntosh
J M
JM
Cruz
L J
LJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D008024:Ligands; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D012908:Snails; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008024:Ligands; D018377:Neurotransmitter Agents; D010455:Peptides; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D004247:DNA; D020866:omega-Conotoxin GVIA