更新于：2024-11-01

N-type calcium channel x Sodium channels

更新于：2024-11-01

基本信息

关联

项与 N-type calcium channel x Sodium channels 相关的药物

JNJ-26990990

靶点

N-type calcium channel x Sodium channels

作用机制

N-type calcium channel抑制剂 [+1]

在研机构

Johnson & Johnson

原研机构

Johnson & Johnson

在研适应症

癫痫

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 N-type calcium channel x Sodium channels 相关的临床结果

登录后查看更多信息

100 项与 N-type calcium channel x Sodium channels 相关的转化医学

登录后查看更多信息

0 项与 N-type calcium channel x Sodium channels 相关的专利（医药）

登录后查看更多信息

项与 N-type calcium channel x Sodium channels 相关的文献（医药）

2006-07-19·Journal of Physics: Condensed Matter3区 · 物理与天体物理

Regulation of membrane protein function by lipid bilayer elasticity—a single molecule technology to measure the bilayer properties experienced by an embedded protein

3区 · 物理与天体物理

Article

作者: Lundbæk, Jens August

Membrane protein function is generally regulated by the molecular composition of the host lipid bilayer. The underlying mechanisms have long remained enigmatic. Some cases involve specific molecular interactions, but very often lipids and other amphiphiles, which are adsorbed to lipid bilayers, regulate a number of structurally unrelated proteins in an apparently non-specific manner. It is well known that changes in the physical properties of a lipid bilayer (e.g., thickness or monolayer spontaneous curvature) can affect the function of an embedded protein. However, the role of such changes, in the general regulation of membrane protein function, is unclear. This is to a large extent due to lack of a generally accepted framework in which to understand the many observations. The present review summarizes studies which have demonstrated that the hydrophobic interactions between a membrane protein and the host lipid bilayer provide an energetic coupling, whereby protein function can be regulated by the bilayer elasticity. The feasibility of this 'hydrophobic coupling mechanism' has been demonstrated using the gramicidin channel, a model membrane protein, in planar lipid bilayers. Using voltage-dependent sodium channels, N-type calcium channels and GABA(A) receptors, it has been shown that membrane protein function in living cells can be regulated by amphiphile induced changes in bilayer elasticity. Using the gramicidin channel as a molecular force transducer, a nanotechnology to measure the elastic properties experienced by an embedded protein has been developed. A theoretical and technological framework, to study the regulation of membrane protein function by lipid bilayer elasticity, has been established.

2004-07-01·Journal of Biological Chemistry2区 · 生物学

A Single Gβ Subunit Locus Controls Cross-talk between Protein Kinase C and G Protein Regulation of N-type Calcium Channels

2区 · 生物学

Article

作者: Brett Simms ; Alexandra E. Kisilevsky ; Gerald W. Zamponi ; Clinton J. Doering ; Wendy Barr ; Aparna Nirdosh ; Zhong-Ping Feng ; Jawed Hamid ; Michelle I. Arnot ; Robert J. Winkfein ; Jean Peloquin

The modulation of N-type calcium channels is a key factor in the control of neurotransmitter release. Whereas N-type channels are inhibited by Gbetagamma subunits in a G protein beta-isoform-dependent manner, channel activity is typically stimulated by activation of protein kinase C (PKC). In addition, there is cross-talk among these pathways, such that PKC-dependent phosphorylation of the Gbetagamma target site on the N-type channel antagonizes subsequent G protein inhibition, albeit only for Gbeta(1)-mediated responses. The molecular mechanisms that control this G protein beta subunit subtype-specific regulation have not been described. Here, we show that G protein inhibition of N-type calcium channels is critically dependent on two separate but adjacent approximately 20-amino acid regions of the Gbeta subunit, plus a highly conserved Asn-Tyr-Val motif. These regions are distinct from those implicated previously in Gbetagamma signaling to other effectors such as G protein-coupled inward rectifier potassium channels, phospholipase beta(2), and adenylyl cyclase, thus raising the possibility that the specificity for G protein signaling to calcium channels might rely on unique G protein structural determinants. In addition, we identify a highly specific locus on the Gbeta(1) subunit that serves as a molecular detector of PKC-dependent phosphorylation of the G protein target site on the N-type channel alpha(1) subunit, thus providing for a molecular basis for G protein-PKC cross-talk. Overall, our results significantly advance our understanding of the molecular details underlying the integration of G protein and PKC signaling pathways at the level of the N-type calcium channel alpha(1) subunit.

1998-11-01·British Journal of Pharmacology2区 · 医学

On the inhibition of voltage activated calcium currents in rat cortical neurones by the neuroprotective agent 619C89

2区 · 医学

Article

作者: G Bernardi ; A Stefani ; A. H. Hainsworth ; F Spadoni

The lamotrigine analogue 619C89, utilised to reduce postischaemic and posttraumatic neuronal injury, has been shown to inhibit sodium channels and cloned N‐type calcium channels. To verify whether this neuroprotective agent also blocked native calcium channels, we have tested its action in cortical pyramidal neurones, acutely isolated from the adult rat brain.

619C89 inhibited more than 90% of the high voltage‐activated calcium currents recorded in the whole‐cell configuration. The response was relatively slow in onset (30–60 s), recovered incompletely (96%), but showed no consistent desensitization.

This inhibitory effect was not selective for any calcium channel subtype, being largely unaffected by ω‐conotoxin‐GVIA, ω‐agatoxin‐IVA, ω‐conotoxin‐MVIIC and dihydropyridine antagonists.

Saturating responses to 619C89 were detected for concentrations 50 μM. Dose‐response curves revealed that 619C89 have an approximately 8 μM binding site.

The effect of 619C89 was dependent on the divalent concentrations in that its potency was reduced on increase of the charge carrier up to 20 mM barium. Since the lamotrigine analogue shifted to the right the dose‐dependence of the cadmium block, the 619C89‐mediated inhibition of calcium currents seemed to rely on a direct interaction with the channel pore. Functional implications are discussed.

British Journal of Pharmacology (1998) 125, 1058–1064; doi:10.1038/sj.bjp.0702134