SINGLE ION CHANNELS IN PANCREATIC ISLET CELLS
SINGLE ION CHANNELS IN PANCREATIC ISLET CELLS
批准号:
3236257
负责人:
STANLEY MISLER
金额:
$11.29万
依托单位国家:
美国
项目类别:
财政年份:
1986
资助国家:
美国
项目状态:
已结题
起止时间:
1986-07-01 至 1989-06-30
中文摘要
内分泌胰腺生理学中一个有趣的问题是,
环境葡萄糖或氨基酸浓度的升高,
无处不在的刺激,所有细胞都暴露于,导致
通过B细胞控制胰岛素的脉冲式分泌和抑制
A细胞分泌胰高血糖素。 这项工作的目标是研究
单离子通道在代谢物刺激物与
胰岛素和胰高血糖素分泌。
主要地,我们希望检查代谢物的刺激是否导致
在B细胞去极化(因此电压依赖性Ca 2+内流)中,
诱导ATP敏感性K+通道的关闭。 为此,我们将
检查该通道的显著特征,包括离子
选择性、门控、单通道动力学和药理学
频道 这些实验将涉及标准细胞的附着和切除
斑片记录、全细胞记录、细胞附着斑片记录,
部分透化的细胞和一种新的“慢”全细胞技术。
第二,我们希望检测B细胞中的细胞内Ca 2+释放,
也可以通过代谢刺激,通过Ca 2+通道发生,
内质网(ER),通过测量Ca 2+通道活性,
融合成平面双层膜的胰岛素瘤ER。 我们还要
确定这种细胞内钙的来源是否有助于
参与触发胰岛素胞吐的Ca 2+池,使用
钙激活的部分心肌细胞贴壁钾通道
透化的细胞作为局部Ca 2+浓度的测定。 三是
我希望开始探索单通道潜在的电活动,
免疫细胞化学鉴定A细胞。
这些实验的结果应该有助于我们了解
内分泌胰腺中的刺激-分泌偶联,并为
糖尿病中膜缺陷的未来研究。
英文摘要
An intriguing question in the physiology of the endocrine pancreas is how a
rise in ambient glucose or amino acid concentration, a seemingly simple and
ubiquitous stimulus which all cells are exposed to, results in the
controlled pulsatile secretion of insulin by the B cell and inhibition of
glucagon secretion by the A cell. The goal of this work is to study the
role of single ion channels in the coupling of metabolite stimuli to
insulin and glucagon secretion.
Principally, we wish to examine whether stimulation by a metabolite results
in B cell depolarization (and hence voltage-dependent Ca2+ influx) by
inducing closure of an ATP sensitive K+ channel. To do this we shall
examine the salient characteristics of this channel including ion
selectivity, gating, single channel kinetics and pharmacology of this
channel. These experiments will involve standard cell attached and excised
patch recording, whole cell recording, cell attached patch recording with
partially permeabilized cells and a novel "slow" whole cell technique.
Second, we wish to examine whether intracellular release of Ca2+ in B cell,
which may also be stimulated by metabolism, occurs through Ca2+ channels in
endoplasmic reticulum (ER), by measuring Ca2+ channel activity of
insulinoma ER fused into planar bilayer membranes. We also wish to
determine whether this source of intracellular calcium contributes to a
pool of Ca2+ which participates in triggering insulin exocytosis, using
Ca2+-activated K+ channels in cell attached patches of partially
permeabilized cells as an assay for local Ca2+ concentration. Third, we
wish to begin exploring single channels underlying electrical activity in
immunocytochemically identified A cells.
Results of these experiments should contribute to our knowledge of
stimulus-secretion coupling in the endocrine pancreas and pave the way for
future investigations of membrane defects in diabetes mellitus.
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ION CHANNELS IN VOLUME REGULATION BY NEUROBLASTOMA CELLS
-
批准号:3414440
-
项目类别:
-
资助金额:$9.34万
-
财政年份:1990
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN VOLUME REGULATION BY NEUROBLASTOMA CELLS
-
批准号:3414438
-
项目类别:
-
资助金额:$10.07万
-
财政年份:1990
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN VOLUME REGULATION BY NEUROBLASTOMA CELLS
-
批准号:3414439
-
项目类别:
-
资助金额:$8.94万
-
财政年份:1990
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN PANCREATIC CELLS
-
批准号:2608408
-
项目类别:
-
资助金额:$15.47万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
SINGLE ION CHANNELS IN PANCREATIC ISLET CELLS
-
批准号:3236254
-
项目类别:
-
资助金额:$10.34万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
SINGLE ION CHANNELS IN PANCREATIC ISLET CELLS
-
批准号:3236258
-
项目类别:
-
资助金额:$11.85万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN PANCREATIC CELLS
-
批准号:2016204
-
项目类别:
-
资助金额:$17.36万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN PANCREATIC ISLET CELLS
-
批准号:2140084
-
项目类别:
-
资助金额:$12.7万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN PANCREATIC CELLS
-
批准号:6124840
-
项目类别:
-
资助金额:$16.41万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN PANCREATIC ISLET CELLS
-
批准号:3236256
-
项目类别:
-
资助金额:$16.84万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN PANCREATIC ISLET CELLS
-
批准号:3236259
-
项目类别:
-
资助金额:$13.33万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN PANCREATIC CELLS
-
批准号:2838089
-
项目类别:
-
资助金额:$15.93万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN PANCREATIC ISLET CELLS
-
批准号:3236260
-
项目类别:
-
资助金额:$11.64万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
ION CHANNELS IN PANCREATIC ISLET CELLS
-
批准号:3236261
-
项目类别:
-
资助金额:$12.11万
-
财政年份:1986
-
负责人:STANLEY MISLER
-
依托单位:
海外基金