Molecular Diversity of K Channels in Cardiovascular System.

心血管系统中 K 通道的分子多样性。

基本信息

批准号：
08044313
负责人：
WATANABE Minoru
金额：
$ 3.65万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08044313/
关键词：
A-type K current smooth muscle RT-PCR technique Kv4.3 HEK 293 cell arachidonic acid Ca^<2+>-dependent K^+ channel voltage-dependent Ca^<2+> channel 早期不活性型K^+電流 Ca^<2+>依存性K^+チャネル L型Ca^<2+>チャネル内向き整流性Kチャネル早期不活性型K電流 Ca依存性Kチャネル

项目摘要

Early inactivating K^+ (A type) current can be recorded widely in neuron, cardiac myocytes and smooth muscle cells. the current plays significant roles for the regulation of action potential firing and formation of the repolarizing phase of an action potential. Although several distinct genes encoding the K^+ channels responsible for A type K^+ current (I_A) in cardiac myocytes and brain have been reported, nothing is known in smooth muscle cells. The electrophysiological characteristics of I_A in smooth muscle cells (vas deferens, colon and ureter) and similar to those in cardiac myocytes. Nevertheless, it was found that arachidonic acid selectively blocks the I_A in smooth muscle cells (Am.J.Physiol.1997). The possibility that the K^+ channel gene for I_A in smooth muscle is deferent from that in cardiac myocytes was examined using RT-PCR techniques. In addition, the related K^+ channels in smooth muscle cells in the rat was cloned. Kv1.4,4.2 and 4.3 have been reported as K^+ channel … More genes in brain and cardiac myocytes. Based on the expression levels of mRNAs of these genes, it was found taht Kv4.3 is predominant among them in smooth muscle cells. Moreover, Kv4.3 in smooth muscle cells was a new spliced variant of the original Kv4.3 (Kv.4.3M) in brain and has additional 19 amino acids in cytosolic domain close to the C terminus (Kv4.3L) (FEBS Letters, 1997). In the rat heart, the mRNA level of Kv4.3L was higher than that of Kv4.3M.Electrophysiological characteristics of Kv1.4,4.2,4.3M and 4.3L K^+ channels were determined in HEK 293 cells in which one of these channel types was highly expressed. The voltage-dependence of activation and inactivation, the recovery time course from inactivation and the sensitivity to arachidonic acid of Kv4.3L were not significantly different from those of Kv4.3M.Further research is required to elucidate the functional roles of additional 19 amino acids in Kv4.3L.It was also found that the different expression levels of mRNAs encoding the large conductance Ca^<2+> -dependent K^+ channels and the voltage-dependent Ca^<2+> channels in various type of smooth muscle cells, at least in part, explains the difference in membrane excitability in different types of smooth muscle cells. Less

早期失活 K^+（A 型）电流可以在神经元、心肌细胞和平滑肌细胞中广泛记录，该电流对于动作电位放电的调节和动作电位复极相的形成起着重要作用。编码负责心肌细胞和大脑中的 A 型 K^+ 电流 (I_A) 的 K^+ 通道的基因已被报道，但平滑肌细胞中 I_A 的电生理特征尚不清楚。输尿管）和心肌细胞中的类似，然而，发现花生四烯酸选择性地阻断平滑肌细胞中的I_A（Am.J.Physiol.1997）平滑肌中I_A的K^+通道基因的可能性。使用RT-PCR技术检查了与心肌细胞中的不同。此外，克隆了大鼠平滑肌细胞中的相关K^+通道。据报道，脑和心肌细胞中存在 K^+ 通道基因。根据这些基因的 mRNA 表达水平，发现 Kv4.3 在平滑肌细胞中占主导地位。平滑肌细胞是大脑中原始Kv4.3（Kv.4.3M）的新剪接变体，在靠近C末端的胞质结构域（Kv4.3L）有额外的19个氨基酸(FEBS Letters, 1997) 在大鼠心脏中，Kv4.3L 的 mRNA 水平高于 Kv4.3M。在 HEK 293 细胞中测定了 Kv1.4、4.2、4.3M 和 4.3L K^+ 的电生理特征。其中这些通道类型之一高度表达激活和失活的电压依赖性、失活的恢复时间过程和敏感性。 Kv4.3L的花生四烯酸与Kv4.3M的花生四烯酸没有显着差异。需要进一步的研究来阐明Kv4.3L中额外的19个氨基酸的功能作用。还发现编码大的mRNA的表达水平不同各种类型平滑肌细胞中电导 Ca^<2+> 依赖性 K^+ 通道和电压依赖性 Ca^<2+> 通道至少部分解释了细胞膜兴奋性的差异。不同类型的平滑肌细胞较少。