Molecular Diversity of K Channels in Cardiovascular System.

心血管系统中 K 通道的分子多样性。

• 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

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）电流广泛存在于神经元、心肌细胞和平滑肌细胞中。电流对于动作电位放电的调节和动作电位的复极化相的形成起重要作用。虽然已经报道了几种编码心肌细胞和脑中A型K^+电流（I_A）的K^+通道的不同基因，但在平滑肌细胞中还一无所知。平滑肌细胞（输精管、结肠和输尿管）的I_A电生理特性与心肌细胞相似。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）。用RT-PCR技术检测了平滑肌和心肌细胞中I_A钾通道基因的可能性。此外，还克隆了大鼠平滑肌细胞中相关的K^+通道。Kv1.4，4.2和4.3已被报道为K^+通道 ...更多信息 脑和心肌细胞中的基因。根据这些基因的mRNA表达水平，发现Kv4.3在平滑肌细胞中占优势。此外，平滑肌细胞中的Kv4.3是脑中原始Kv4.3（Kv.4.3M）的新剪接变体，并且在靠近C末端的胞质结构域中具有额外的19个氨基酸（Kv4.3L）（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钾通道的电生理特性。激活和失活的电压依赖性，Kv4.3L的失活恢复时间和对花生四烯酸的敏感性与Kv4.3M无显著差异，Kv4.3L中另外19个氨基酸的功能作用有待进一步研究。不同类型平滑肌细胞中的电压依赖性Ca^2+通道和电压依赖性Ca^2+通道的差异，至少部分地解释了不同类型平滑肌细胞中膜兴奋性的差异。少

项目成果

Yoshiaki Uyama et al.: "Inhibition by calponin of isomettic force in demembranated vascular smooth musscle strips : the critical role of serine-175" Biochemical Journal. 319. 551-558 (1996)

Yoshiaki Uyama 等人：“钙调蛋白对去膜血管平滑肌条等长力的抑制：丝氨酸 175 的关键作用”生物化学杂志。

K.Muraki et al.: "Apamine-sensitive Ca^<2+>-dependent K^+ current and hyperpolarization in human endothelial cells." Biochem.Biophys.Res.Commun.236. 340-343 (1997)

K.Muraki等人：“人内皮细胞中阿帕胺敏感的Ca^2依赖性K^电流和超极化。”

S:Ohya et al.: "Molecular clonino and tissue distripution of an alterhatively spliced variant of an A-type K^+ channel x-supunit,Kv4.3 in the rat." FEBS Letters. 420. 47-53 (1997)

S：Ohya 等人：“大鼠中 A 型 K 通道 x-supunit，Kv4.3 的选择性剪接变体的分子克隆和组织分布。”

Notihiro Nagano et al.: "Effects of utachidonic acid on A-type potassium eurrents in smoth muscle cells of the quinea pig." Ametican Joutnal of Physiology. 272. (1997)

Notihiro Nagano 等人：“花生四烯酸对豚鼠平滑肌细胞 A 型钾电流的影响。”

Y.Uyama et al.: "Inhibition by calponin of isometric force in demembrahated vascular smooth muscle strips i the control of serine-175" Biochemical Journal. 319. 551-558 (1996)

Y.Uyama 等人：“在丝氨酸 175 的控制下，钙调蛋白对去膜血管平滑肌条中等长力的抑制”生物化学杂志。