SODIUM AND CATION CHANNELS IN CYSTIC FIBROSIS
囊性纤维化中的钠和阳离子通道
基本信息
- 批准号:6239176
- 负责人:
- 金额:$ 12.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-09-29 至 1998-08-31
- 项目状态:已结题
- 来源:
- 关键词:Xenopus oocyte chloride channels cystic fibrosis gastrointestinal epithelium human genetic material tag immunocytochemistry in situ hybridization inhibitor /antagonist ion transport laboratory rat membrane channels membrane permeability membrane potentials molecular biology molecular cloning molecular pathology pancreatic islets pharmacology respiratory epithelium sodium sodium channel sweat glands transfection
项目摘要
Although we know that the rectifying chloride channel is defective when
mutant CFTR is expressed, the relationship between the cystic fibrosis
transmembrane conductance regulator (CFTR) and other ion channels in
cystic fibrosis (CF) tissues is not known. Cystic fibrosis (CF) is also
characterized by increased sodium absorption. This increased sodium
absorption adds to the reduced chloride secretion to further diminish
normal fluid balance. If sodium hyperabsorption or normal sodium
absorption can be inhibited, it may mitigate compromised fluid balance.
The cellular basis of the sodium defect in CF is unknown. One
possibility is increased absorption through amiloride-sensitive sodium
channels. Since nucleotide-gated cation channels are abundantly
expressed in lung (bronchi and bronchioles) and gut, (villus cells), two
organs involved in cystic fibrosis, this channel may also contribute to
hyperabsorption of sodium. If nucleotide-gated cation channels
participate in normal sodium absorption or excessive sodium absorption
in CF, the dichlorobenzamil inhibitory site on this channel may be a
potential site for therapeutic intervention. The Specific Aims are: 1)
To evaluate whether nucleotide-gated cation channels contribute to sodium
absorption in tissues involved in CF by determining a) the distribution
of nucleotide-gated channels by in situ hybridization in normal seat
glands, pancreatic cells and the nasal epithelium b) immunocytochemical
localization of the channel in lung, intestine, pancreas and sweat glands
and c) the contribution of nucleotide-gated channels to short circuit
current of rat tracheal cells. 2) To evaluate the interaction between
amiloride-sensitive sodium channels and nucleotide-gated cation channels
and CFTR by cotransfection of nucleotide-gated channels with mutated or
normal CFTR for study of the properties of channels which may be
responsible for hyperabsorption of sodium. Comparisons will be made
using whole-cell and single channel recordings. 3) To clone, then
characterize the pharmacological and electrophysiological properties of
the novel intestinal nucleotide-gated cation channel by expression of
cDNA clone(s) in oocytes. To determine if dichlorobenzamil blocks the
condition pore of the nucleotide-gated channel.
尽管我们知道整流氯离子通道在以下情况下是有缺陷的:
突变CFTR表达与囊性纤维化的关系
跨膜电导调节器(CFTR)和其他离子通道
囊性纤维化(CF)组织尚不清楚。 囊性纤维化(CF)也
其特点是钠吸收增加。 这增加了钠
吸收会增加氯离子分泌的减少,从而进一步减少
正常的液体平衡。 如果钠吸收过度或钠正常
吸收可以被抑制,它可以减轻液体平衡的损害。
CF 中钠缺陷的细胞基础尚不清楚。 一
可能是通过阿米洛利敏感的钠增加吸收
渠道。 由于核苷酸门控阳离子通道丰富
在肺(支气管和细支气管)和肠道(绒毛细胞)中表达,两种
参与囊性纤维化的器官,该通道也可能有助于
钠吸收过度。 如果核苷酸门控阳离子通道
参与正常钠吸收或过量钠吸收
在CF中,该通道上的二氯苯甲酰胺抑制位点可能是
治疗干预的潜在位点。 具体目标是:1)
评估核苷酸门控阳离子通道是否对钠有贡献
CF 相关组织的吸收,通过确定 a) 分布
通过正常位点原位杂交构建核苷酸门控通道
腺体、胰腺细胞和鼻上皮 b) 免疫细胞化学
通道在肺、肠、胰腺和汗腺中的定位
c) 核苷酸门控通道对短路的贡献
大鼠气管细胞电流。 2)评估之间的相互作用
阿米洛利敏感钠通道和核苷酸门控阳离子通道
和 CFTR 通过共转染核苷酸门控通道与突变或
正常 CFTR 用于研究通道的特性,可能是
负责钠的过度吸收。 将会进行比较
使用全细胞和单通道记录。 3)克隆,然后
表征药理学和电生理学特性
通过表达新型肠道核苷酸门控阳离子通道
卵母细胞中的 cDNA 克隆。 确定二氯苯甲酰胺是否阻断
核苷酸门控通道的条件孔。
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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SANDRA ELIZABETH GUGGINO其他文献
SANDRA ELIZABETH GUGGINO的其他文献
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{{ truncateString('SANDRA ELIZABETH GUGGINO', 18)}}的其他基金
Role of C1C5 in Endocytosis and NHE3 Trafficking
C1C5 在内吞作用和 NHE3 运输中的作用
- 批准号:
7487971 - 财政年份:2007
- 资助金额:
$ 12.76万 - 项目类别:
Role of C1C5 in Endocytosis and NHE3 Trafficking
C1C5 在内吞作用和 NHE3 运输中的作用
- 批准号:
7133530 - 财政年份:2006
- 资助金额:
$ 12.76万 - 项目类别:
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