MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CA CHANNEL
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CA CHANNEL
批准号:
3288137
负责人:
STANLEY M GOLDIN
金额:
$16.93万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1985
资助国家:
美国
项目状态:
已结题
起止时间:
1985-09-27 至 1992-01-31
关键词:
acetylcholine axon brain calcium channel calcium transporting ATPase cations cow cyclic GMP density gradient ultracentrifugation diltiazem high performance liquid chromatography isomer membrane potentials membrane proteins membrane reconstitution /synthesis protein structure radiotracer synaptosomes transport proteins visual photoreceptor
中文摘要
最近观察到鸟苷3‘:5’环
一磷酸(“cGMP”)激活外膜的阳离子通道
脊椎动物视杆感光细胞的片段。我们的实验室
已经开发出一种从牛盘中提纯的程序
Rod路由器分段,并演示了这样的通道是
与光盘相关联。当被cGMP激活时,该频道可以
快速释放钙离子池,这些钙离子由
盘相关的、依赖于ATP的钙离子泵。CGMP和cGMP
Ca~(++)对杆状细胞膜电位有调制作用
外段质膜,以及光引发的事件
戏剧性地改变cGMP的代谢;这表明
CGMP激活的视盘通道可能是
光感受器电的短期和/或长期调节
活动。我们的目标是进一步刻画、重组和
净化这个cGMP激活的通道。
为了定量地表征活性、药理学和
通道的电导特性,我们将采用--和
进一步完善--快速动力学测量的新方法
通道活动。所提出的RAPAID动力学技术可能是
离子通道驻留特性的一般适用性
在细胞器中太小而不能应用
电生理方法,如膜片钳。
为了净化光盘通道,我们将采用一种新的方法
实验室已经开发出--“运输专用分馏”--
与其他膜蛋白纯化方法相结合。
转运专一性分离利用膜的重建
将蛋白质运输到脂质体中作为运输的物理工具
以功能活性形式纯化蛋白质。身份识别
相关的激动剂和拮抗剂结合位点将是一个
监视信道重建的附加手段以及
净化。
先前记录的cGMP在其他领域的调节作用
系统似乎是由磷酸激酶酶介导的;相反,有
是强烈的迹象表明与光盘相关的频道-和
杆状突起在杆状突起的质膜上的相似或相同的突起
片段--由cGMP直接激活。重组和
净化后的通道应能使使用人员严格检测
这一重要的新假说。
英文摘要
It has recently been observed that guanosine 3':5' cyclic
monophosphate ("cGMP") activates cation channels in the outer
segments of vertebrate rod photoreceptor cells. Our laboratory
has developed a procedure for purification of discs from bovine
rod outer segments, and demonstrated that such a channel is
associated with discs. When activated by cGMP, the channel can
rapidly discharge a pool of Ca++ that is actively accumulated by a
disc- associated, ATP-dependent Ca++ pump. Both cGMP and
Ca++ are capable of modulating the membrane potential of rod
outer segment plasma membranes, and light initiaties events that
dramatically alter cGMP metabolism; this suggests that the
cGMP-activated channel of discs may be an important link in the
short and/or long term regulation of photoreceptor electrical
activity. Our goals are to further characterize, reconstitute and
purify this cGMP-activated channel.
To quantitatively characterize the activation, pharmacology, and
conductance properties of the channel, we will employ-- and
further refine-- new approaches for rapid kinetic measurement of
channel activity. The propsed rapaid kinetic techniques may be of
general applicability for characterization of ion channels residing
in organelles that are too small for application of
electrophysiological methods such as patch clamping.
To purify the disc channel, we will employ a novel approach this
laboratroy has developed--"transport- specific fractionation"--
together with other methods for membrane protein purification.
Transport-specific fractionation uses reconstitution of membrane
transport proteins into liposomes as a physical tool for transport
protein purification in functionally active form. Identification of
the associated agoinst and antagonist binding sites will be an
additional means of monitoring the channel's reconstitution and
purification.
Previously documented regulatory effects of cGMP In other
systems appear to be phosphokinases- mediated; in contrast, there
are strong indications that both the disc-associated channel-- and
a similar or identical one in the plasma membrane of rod other
segments-- are directly activated by cGMP. Reconstitution and
purification of the channel should enable use to rigorously test
this important new hypothesis.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
SYNTHETIC NEUROPROTECTIVE GLUTAMATE RELEASE BLOCKERS
-
批准号:3504569
-
项目类别:
-
资助金额:$5.0万
-
财政年份:1991
-
负责人:STANLEY M GOLDIN
-
依托单位:
SYNTHETIC NEUROPROTECTIVE GLUTAMATE RELEASE BLOCKERS
-
批准号:3509292
-
项目类别:
-
资助金额:$25.0万
-
财政年份:1991
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CHANNEL
-
批准号:3288141
-
项目类别:
-
资助金额:$11.5万
-
财政年份:1989
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CHANNEL
-
批准号:3288140
-
项目类别:
-
资助金额:$27.2万
-
财政年份:1989
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CHANNEL
-
批准号:3288139
-
项目类别:
-
资助金额:$22.71万
-
财政年份:1989
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CA CHANNEL
-
批准号:3288138
-
项目类别:
-
资助金额:$1.43万
-
财政年份:1985
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR STUDIES OF CA++ TRANSPORT IN NERVE AND RETINA
-
批准号:3288136
-
项目类别:
-
资助金额:$8.71万
-
财政年份:1985
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR STUDIES OF CA++ TRANSPORT IN NERVE AND RETINA
-
批准号:3288142
-
项目类别:
-
资助金额:$21.59万
-
财政年份:1985
-
负责人:STANLEY M GOLDIN
-
依托单位:
MOLECULAR PROPERTIES OF A CGMP-ACTIVATED CA CHANNEL
-
批准号:3288135
-
项目类别:
-
资助金额:$17.84万
-
财政年份:1985
-
负责人:STANLEY M GOLDIN
-
依托单位:
PHARMACOLOGICAL SCIENCES
-
批准号:3537213
-
项目类别:
-
资助金额:$10.5万
-
财政年份:1975
-
负责人:STANLEY M GOLDIN
-
依托单位:
PHARMACOLOGICAL SCIENCES
-
批准号:3537215
-
项目类别:
-
资助金额:$10.56万
-
财政年份:1975
-
负责人:STANLEY M GOLDIN
-
依托单位:
PHARMACOLOGICAL SCIENCES
-
批准号:3537217
-
项目类别:
-
资助金额:$20.92万
-
财政年份:1975
-
负责人:STANLEY M GOLDIN
-
依托单位:
PHARMACOLOGICAL SCIENCES
-
批准号:3537216
-
项目类别:
-
资助金额:$20.92万
-
财政年份:1975
-
负责人:STANLEY M GOLDIN
-
依托单位:
海外基金