A NEW CONUS PEPTIDE LIGAND FOR MAMMALIAN PRESYNAPTIC CA2+ CHANNELS

被引:463
作者
HILLYARD, DR
MONJE, VD
MINTZ, IM
BEAN, BP
NADASDI, L
RAMACHANDRAN, J
MILJANICH, G
AZIMIZOONOOZ, A
MCINTOSH, JM
CRUZ, LJ
IMPERIAL, JS
OLIVERA, BM
机构
[1] UNIV UTAH,DEPT PATHOL,SALT LAKE CITY,UT 84132
[2] UNIV UTAH,DEPT PSYCHIAT,SALT LAKE CITY,UT 84132
[3] HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115
[4] UNIV PHILIPPINES,INST CHEM,QUEZON CITY 1107,PHILIPPINES
[5] UNIV PHILIPPINES,INST MARINE SCI,QUEZON CITY 1107,PHILIPPINES
[6] NEUREX CORP,MENLO PK,CA 94025
关键词
D O I
10.1016/0896-6273(92)90221-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 Ca-45(2+) 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.
引用
收藏
页码:69 / 77
页数:9
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