REGULATION OF SODIUM CHANNEL DISTRIBUTION IN NEURONAL CELLS
神经细胞钠通道分布的调节
基本信息
- 批准号:6205058
- 负责人:
- 金额:$ 13.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-08-01 至 2000-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Recombinant DNA approaches have revealed that voltage gated sodium
channels exist as a number of distinct isoforms. There is evidence
that some excitable cells express multiple channel isoforms that
are targeted to different cellular areas. This project addresses
the hypothesis that peripheral nervous system (PNS) channel
isoforms have distinct structural properties that allow them to be
differentially targeted to appropriate membrane domains in
peripheral neurons and their processes. There are three specific
aims: 1) The cellular and subcellular distribution of PNS-abundant
sodium channel isoforms will be established using
immunocytochemical techniques. Isoform specific antibodies will be
produced and used to establish the protein distribution of co-
expressed isoforms in the nervous system of the rat. Of particular
interest will be the identification of the predominant channel
isotypes in the different cell types of peripheral ganglia and
those that inhabit nodes of Ranvier in myelinated fibers of the
PNS. 2) A peripheral neuron paradigm will be developed that will
allow molecular manipulation of isoform expression and structure,
The PC12 cell line will be studied as a possible model for
selective targeting of channel isoforms to cell bodies and
processes. Primary cultures of dorsal root and superior cervical
ganglion neurons will similarly be investigated for their
suitability in these studies. Each system will be assessed for the
ability to control selectively wild-type isoform expression and to
express mutant channel isoforms. 3) Channel isoform domains that
specify targeting properties and the moieties that interact with
them will be characterized. Candidate targeting domains will be
identified by comparing primary sequences among channels whose
targeting differs. The role of these domains in targeting will be
tested through mutagenesis and chimeric construct alteration of
their structure. These domains will then serve as the basis for
identification of accessory molecules that assist in the targeting
process. In a health context, this project will address cellular
and molecular processes that strongly relate to the treatment of
chronic pain and the dysfunction experienced in demyelinative
disorders of the CNS and PNS.
重组DNA方法揭示了电压门控钠
通道以多种不同的亚型存在。有证据表明
一些可兴奋的细胞表达多种通道异构体,
针对不同的细胞区域。本项目致力于
周围神经系统(PNS)通道的假说
异构体具有不同的结构属性,这使得它们能够
不同地靶向适当的膜结构域
外周神经元及其突起。有三个具体的
目的:1)丰富的三七总皂苷在细胞和亚细胞中的分布
钠通道异构体的建立将使用
免疫细胞化学技术。亚型特异性抗体将是
生产并用于建立共同的蛋白质分布
在大鼠神经系统中表达的异构体。特别的
感兴趣的将是主要渠道的标识
外周神经节不同细胞类型的同工型
分布于有髓神经纤维中的兰维尔结节
PNS。2)将开发一种外周神经元范例,
允许异构体表达和结构的分子操作,
PC12细胞系将作为一种可能的模型进行研究
通道异构体选择性靶向细胞体和
流程。背根和上颈椎的原代培养
同样地,神经节神经元也将被研究
在这些研究中的适用性。将对每个系统进行评估,以
选择性地控制野生型异构体表达和
表达突变的通道亚型。3)通道异构体结构域
指定目标属性和与其交互的部分
它们将被刻画出来。候选目标域将是
通过比较以下通道之间的主序列来识别
目标不同。这些领域在目标定位方面的作用将是
经诱变和嵌合结构改变检测
他们的结构。然后,这些域将作为
辅助靶向的辅助分子的鉴定
进程。在健康方面,该项目将解决蜂窝
以及与疾病治疗密切相关的分子过程
慢性疼痛与脱髓鞘患者的功能障碍
中枢神经系统和三叉神经节障碍。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Simon R LEVINSON其他文献
Simon R LEVINSON的其他文献
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{{ truncateString('Simon R LEVINSON', 18)}}的其他基金
REGULATION OF SODIUM CHANNEL DISTRIBUTION IN NEURONAL CELLS
神经细胞钠通道分布的调节
- 批准号:
6338954 - 财政年份:2000
- 资助金额:
$ 13.51万 - 项目类别:
CLUSTER OF VOLTAGE SENSITIVE NA CHANNELS ON AXONS IS INDEPENDENT OF SCHWANN CELL
轴突上的电压敏感 NA 通道簇独立于施万细胞
- 批准号:
6121831 - 财政年份:1999
- 资助金额:
$ 13.51万 - 项目类别:
REGULATION OF SODIUM CHANNEL DISTRIBUTION IN NEURONAL CELLS
神经细胞钠通道分布的调节
- 批准号:
6112562 - 财政年份:1998
- 资助金额:
$ 13.51万 - 项目类别:
CLUSTER OF VOLTAGE SENSITIVE NA CHANNELS ON AXONS IS INDEPENDENT OF SCHWANN CELL
轴突上的电压敏感 NA 通道簇独立于施万细胞
- 批准号:
6282144 - 财政年份:1998
- 资助金额:
$ 13.51万 - 项目类别:
REGULATION OF SODIUM CHANNEL DISTRIBUTION IN NEURONAL CELLS
神经细胞钠通道分布的调节
- 批准号:
6243855 - 财政年份:1997
- 资助金额:
$ 13.51万 - 项目类别:
CLUSTERING OF NA CHANNELS ON AXONS IS INDEPENDENT OF DIRECT SCHWANN CELL CONTACT
轴突上 NA 通道的聚集独立于施万细胞的直接接触
- 批准号:
6252944 - 财政年份:1997
- 资助金额:
$ 13.51万 - 项目类别:
MECHANISMS OF THE VOLTAGE-DEPENDENT SODIUM CHANNEL
电压依赖性钠通道的机制
- 批准号:
6186974 - 财政年份:1993
- 资助金额:
$ 13.51万 - 项目类别:
MECHANISMS OF THE VOLTAGE-DEPENDENT SODIUM CHANNEL
电压依赖性钠通道的机制
- 批准号:
2262903 - 财政年份:1993
- 资助金额:
$ 13.51万 - 项目类别:
MECHANISMS OF THE VOLTAGE-DEPENDENT SODIUM CHANNEL
电压依赖性钠通道的机制
- 批准号:
2891582 - 财政年份:1993
- 资助金额:
$ 13.51万 - 项目类别:
MECHANISMS OF THE VOLTAGE-DEPENDENT SODIUM CHANNEL
电压依赖性钠通道的机制
- 批准号:
2262901 - 财政年份:1993
- 资助金额:
$ 13.51万 - 项目类别: