Electropharmacological analysis of the signal transduction mechanisms of the delayd rectifier potassium channel of heart cells.

心脏细胞延迟整流钾通道信号转导机制的电药理学分析

• 批准号: 03454141
• 负责人: IIJIMA Toshihiko
• 金额: $ 3.78万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454141/
• 关键词: Ventricular cells; Patch-clamp method; Adenylate cyclase; Forskolin derivative; Delayd rectifier K^+ current; L-type Ca^<2+> current; Aortic endothelial cell; intracellular Ca^<2+>; 単離心室筋細胞; 細胞内情報伝達機構; L型カルシウムイオンチャンネル; 遅延整流カリウムイオンチャンネル; フォルスコリ

This study was designed to investigate the differential modulation of the L-type Ca^<2+> (I_<Ca>) and the delayd rectifier K^+ current (I_K) by direct activation of adenylate cyclase in guinea pig ventricular cells. Isoproterenol equally and simultaneously increased both I_<Ca> and I_K in a same threshold concentration, but a water soluble forskolin derivative, NKH477, increased I_K at lower threshold concentrations than that for increasing I_<Ca>. Selective stimulation of beta-1 adrenoceptors, on the other hand, elicited an increase in I_<Ca> more sensitively than I_K. These results suggest that a simple signal transduction pathway from beta adrenoceptors to I_<Ca> and I_K channels mediated through adenylate cyclase and cyclic AMP-dependent protein kinase is not sufficient to explain these differences. It is, therefore, concluded that I_<Ca> and I_K channels could be differentially regulated during beta adrenoceptor stimulation.Mechanisms responsible for the sustained elevation in intracellular free Ca^<2+> concentration ([Ca^<2+>]_i) in response to histamine and ATP were also studied in cultured human aortic endothelial cells loaded with the fluorescent Ca^<2+> indicator fura-2. Results indicate that the sustained elevation of [Ca^<2+>]_i is resulted from the Cl^--sensitive entry of extracellular Ca^<2+> in human aortic endothelial cells.

这项研究旨在通过在豚鼠心室细胞中直接激活腺苷酸环化酶来研究L型Ca^<2+>（I_ <ca>）和延迟整流k^+电流（I_K）的差异调节。异丙肾上腺素同时同时增加了I_ <ca>和I_K的阈值浓度，但是在较低的阈值浓度下，水溶性的forskolin衍生物NKH477增加了I_K，而I_K的浓度低于增加I_ <ca>。另一方面，选择性刺激β-1肾上腺素受体会引起I_ <ca>的增加，比I_K更敏感。这些结果表明，从β肾上腺素受体到I_ <ca>的简单信号转导途径和通过腺苷酸环化酶和环状AMP依赖性蛋白激酶介导的I_K通道不足以解释这些差异。因此，得出的结论是，I_ <ca>和I_K频道可能在β肾上腺素受体刺激期间受到差异调节。机构在培养的ca和ATP响应的培养物中，还研究了培养的ca erte <2+ca <ca e+ca y+ca < Fura-2。结果表明，[Ca^<2+>] i的持续升高是由人主动脉内皮细胞中细胞外Ca^<2+>的敏感进入产生的。

项目成果

K.Harada and T.Iijima: "Differential modulation by adenylate cyclase of Ca2^+ and delayed K^+ current in ventricular myocytes."

K.Harada 和 T.Iijima：“腺苷酸环化酶对心室肌细胞中 Ca2^ 的差异调节和延迟的 K^ 电流。”

Hosoki,E.: "Chloride-sensitive Ca^<2+> entry by histamine and ATP in human aortic endothelial cells." European Journal of Pharmacoloqy(Molecular pharmacoloqy Section). 266. 213-218 (1994)

Hosoki,E.：“人主动脉内皮细胞中组胺和 ATP 对氯化物敏感的 Ca^2 进入”。

K.Harada & T.Iijima: "Differential modulation by adenylate cyclase of Ca^<2+> and delayd K^+ current in ventricular myocytes." Am.J.Physiol. in press. (1994)

原田健

T.Iijima,M.Hosono and N.Taira: "Electropharmacological analysis of the forskolin binding site on adenylate cyclase in single ventricular cells of the guinea-pig heart."

T.Iijima、M.Hosono 和 N.Taira：“豚鼠心脏单心室细胞中腺苷酸环化酶上毛喉素结合位点的电药理学分析。”

E.Hosoki and T.Iijima: "Chloride-sensitive calcium entry by histamine and ATP in human aortic endothelial cells."

E.Hosoki 和 T.Iijima：“人主动脉内皮细胞中组胺和 ATP 对氯离子敏感的钙进入。”