STRUCTURE AND FUNCTIONAL EXPRESSION OF AN OMEGA-CONOTOXIN SENSITIVE HUMAN N-TYPE CALCIUM-CHANNEL

被引：463

作者：

WILLIAMS, ME ^{[1
]}

BRUST, PF ^{[1
]}

FELDMAN, DH ^{[1
]}

PATTHI, S ^{[1
]}

SIMERSON, S ^{[1
]}

MAROUFI, A ^{[1
]}

MCCUE, AF ^{[1
]}

VELICELEBI, G ^{[1
]}

ELLIS, SB ^{[1
]}

HARPOLD, MM ^{[1
]}

机构：

[1] SIBIA INC,505 COAST BLVD S,LA JOLLA,CA 92037

来源：

SCIENCE | 1992年 / 257卷 / 5068期

关键词：

D O I：

10.1126/science.1321501

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

N-type calcium channels are omega-conotoxin (omega-CgTx)-sensitive, voltage-dependent ion channels involved in the control of neurotransmitter release from neurons. Multiple subtypes of voltage-dependent calcium channel complexes exist, and it is the alpha-1 subunit of the complex that forms the pore through which calcium enters the cell. The primary structures of human neuronal calcium channel alpha-1B subunits were deduced by the characterization of overlapping complementary DNAs. Two forms (alpha-1B-1 and alpha-1B-2) were identified in human neuroblastoma (IMR32) cells and in the central nervous system, but not in skeletal muscle or aorta tissues. The alpha-1B-1 subunit directs the recombinant expression of N-type calcium channel activity when it is transiently co-expressed with human neuronal beta-2 and alpha-2b subunits in mammalian HEK293 cells. The recombinant channel was irreversibly blocked by omega-CgTx but was insensitive to dihydropyridines. The alpha-1B-1-alpha-2b-beta-2-transfected cells displayed a single class of saturable, high-affinity (dissociation constant = 55 pM) omega-CgTx binding sites. Co-expression of the beta-2 subunit was necessary for N-type channel activity, whereas the alpha-2b subunit appeared to modulate the expression of the channel. The heterogeneity of alpha-1B subunits, along with the heterogeneity of alpha-2 and beta-subunits, is consistent with multiple, biophysically distinct N-type calcium channels.

引用

页码：389 / 395

页数：7

共 43 条

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