Title: Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel
Article Preview :

N-type calcium channels are w-conotoxin (w-Cg Tx)-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.sub. 1] submit of the complex that forms the pore through which calcium enters the cell. The primary structures of human neuronal calcium channel [alpha.sub.1B] submits were enters the cell. The primary structures of human neuronal calcium channel [alpha.sub.1B] subunits were deduced by the characterization of overlapping complementary DNAs. Two forms ([alpha.sub.1B-1] and [alpha.sub.1B-2]) were identified in human neuroblastoma (IMR32) cells and in the central nervous systems, but not in skeletal muscle or aorta tissues. The [alpha.sub.1B-1] subunit directs the recombinant expression of N-type calcium channel activity when it is transiently co-expressed with human neuronal [Beta.sub.2] and [alpha.sub.2b] subunits in mammalian HEK293 cells. The recombinant channel was irreversibly blocked by w-Cg Tx but was insensitive to dihydropyrodines. The [alpha.sub.1B-1] [alpha.sub.2b] [Beta.sub.2-] transfected cells displayed a single class of saturable, high-affinity (dissociation constant = 55 pM) w-Cg Tx binding sites. Co-expression of the [Beta.sub.2} subunit was necessary for N-Type channel activity, whereas the [alpha.sub.2b] subunit appeared to modulate the expression of the channel. The heterogeneity of [alpha.sub.1B] subunits, along with the heterogeneity of [alpha.sub.2] and [Beta] subunits, is consistent with multiple, biophysically distinct N-type calcium channels. Voltage-dependent Ca. sup.2+] channels are multisubunit complexes through which extracellular [Ca.sup.2+] enters excitable cells. In rabbit skeletal muscle, for tightly coupled subunits, [alpha.sub.1], [alpha.sub.2], [Beta], and [gamma], make up the channel complex[1]. The primary structure of each subunit has been determined and [alpha.sub.1], [alpha.sub.2], and [Beta] cDNAs have been used to characterize transcripts expressed in other tissues[2]. The [alpha.sub.1] and [Beta] subunits are each encoded by a gene family, including at least five distinct genes for [alpha.sub.1] subunits and three genes for [Beta] subunits[3-6]. Primary transcripts of each of the [alpha.sub.1] genes, the [alpha.sub.2] gene, and two of the [Beta] genes have been shown to yield multiple, structurally distinct, subunits by means of differential processing [6-9]. Expression studies have shown that the [alpha.sub.1] subunits forms the pore through which [Ca.sup.2+] enters the cell [10, 11]. On the basis of biophysical and pharmacological characteristics, three subtypes of neuronal, high-voltage-activated [Ca.sup.2+] channels (L-, N-, and P-type) have been proposed[2]. These high-voltage-activated subtypes are most readily distinguished pharmacologically. The neuronal L-Type channel is dihydropyradine (DHP)-sensitive and, in some cases, reversibly blocked by w-conotoxin (w-CgTX)[12, 13], the N-type channel is DHP-insensitive and irreversibly blocked by w-CgTx[14], and the P-type channel is both DHP- and w-CgTx-insensitive but is sensitive to toxins in venom from funnel web spiders[15]. Recently, recombinant expression of neuronal [Ca.sup.2+] channels was used to identify a high-voltage-activated, DHP,sensitive [Ca.sup.2+] channel that was reversibly blocked by w-CgTx (classified as an L-Type channel) [8] and a DHP-, w-CgTx-sensitive [Ca.sup.2+] channel (possibly a P-type channel)[11]. Co-expression of [alpha.sub.1] and [Beta] subunits is necessary for substantial functional expression of both [Ca.sup.2+] channel subtypes, whereas addition of an [alpha.sub.2] subunit increases the magnitude of the functional response. Much evidence indicates that...
Source Citation (MLA 8 th Edition)
Williams, Mark E., et al. "Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel." Science, vol. 257, no. 5068, 1992, p. 389+. Academic OneFile, Accessed 16 Oct. 2018.

You Are Viewing A Preview Page of the Full ArticleThe article found is from the Gale Academic OneFile database.

You may need to log in through your institution or contact your library to obtain proper credentials.