ROLE OF PROTEIN KINASE C IN REGULATION OF CARDIAC L-TYPE Ca^<2+> CHANNELS.

蛋白激酶 C 在调节心脏 L 型 Ca^2 通道中的作用。

• 批准号: 04670105
• 负责人: KANNO Morio
• 金额: $ 1.34万
• 依托单位: HOKKAIDO UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670105/
• 关键词: L-Type Cardiac Channel; Cell-attached patch; Phorbolestar; TPA; Endothelim-1; Protein kinase C; Rabbit; Cardiomyceste; ウサギ心筋細胞; エンドセリン; Cキナーゼ; ホルボールエステル類

Recordings of single channel activities of cardiac l-type Ca^<2+> channels using a cell-attached patch clamp technique, and subsequent analvses of the recordings were confirmed to be sufficiently applicable to the present study aiming to determine whether cardiac protein kinase C( PKC) participates in regulating cardiac L-type Ca^<2+> channels.The present study using isolated rabbit ventricular myocytes revealed that 12-0-tetradecanoyl phoorbol-13-acetate(TPA), a direct activator of PRC.did not affect single Ca^<2+> channel activities, the result being consistent with the reported data showing no influence on macroscopic Ca2+ currents which was recorded by means of a whole-cell patch clamp technique. Endothelin-1(ET-1) which is known to activate PKC through PIP_2 hydrolvsis after activation of cardiac ET receptors, was also found not to givesignificant influence on the single Ca^<2+> channel activities.These facls cleary indicate that activation of cardiac PKC.even if it occurs directly or indirecily through a receptor mechanism. is not rsponsible to instantaneous regulation of L-type Ca^<2+> channels. differing from the cAMP-A kinase system.However. these findings contradict the fact that ET-1 is able to establish a PKC inhibitor(H-7, sta urosporine)-suppressible, nifedipine-sensitive delayd pnase of positive inotropic effect in guiea pig atria.PKC activation, not instantaneously but through a long range pathway of intracellular signal transducing process, may have a role in regulating 1-type Ca^<2+> channels by either inhibition of dephosphrylation or recruitement of sleeping Ca2+ channels.

利用细胞贴附膜片钳技术记录心脏l型Ca^<2+>通道的单通道活动，并对记录进行后续分析，证实这些记录足以适用于本研究，旨在确定心脏蛋白激酶C（PKC）是否参与调节心脏l型Ca^<2+>通道。本研究通过分离兔心室肌细胞发现了PRC的直接激活剂- 12-0-十四烷醇磷酸-13-乙酸（TPA）。不影响单个Ca^<2+>通道活动，结果与报告的数据一致，显示对通过全细胞膜片钳技术记录的宏观Ca2+电流没有影响。已知内皮素-1（ET-1）在激活心脏ET受体后通过PIP_2水解激活PKC，也被发现对单个Ca^<2+>通道活性没有显著影响。这些因素清楚地表明心脏PKC的激活。即使它直接或间接地通过受体机制发生。不负责l型Ca^<2+>通道的瞬时调节。与cAMP-A激酶系统不同，然而。这些发现与ET-1能够在豚鼠心房中建立PKC抑制剂（H-7, sta urosporine）抑制、硝苯地平敏感的正性肌力延迟酶的事实相矛盾。PKC的激活，不是瞬间的，而是通过细胞内信号转导过程的长期途径，可能通过抑制去磷酸化或募集睡眠Ca2+通道来调节1型Ca^<2+>通道。

项目成果

武田洋司: "ジヒドロピリジン系Ca^<2+>チャネルアゴニストの心筋L型Ca^<2+>チャネルに対する膜電位依存性" 心電図. 12. 574 (1992)

Yoji Takeda：“二氢吡啶 Ca ^ 2+ 通道激动剂对心肌 L 型 Ca ^ 2+ 通道的膜电位依赖性”心电图。 12. 574 (1992)

Hattori Y., et al.: "A dual-component positive inotropic effect of endothelin-1 in guinea pig atria : A role of protein kinase." J.Pharmacol.Exp.Ther.266. 1202-1212 (1993)

Hattori Y. 等人：“内皮素 1 在豚鼠心房中的双重正性肌力作用：蛋白激酶的作用。”

Tohse N., et al.: "Cyclic GMP-mediated ingibition of L-type Ca^<2+> channel activity by human natriuretic peptide in rabbit heart." Submitted to Circulation Research. (1994)

Tohse N.等人：“兔心脏中人利尿钠肽对L型Ca^2通道活性的循环GMP介导的激发”。

Hattori Y.,et al.: "A dual-component positive inotropic effect of endothelin-1 in guinea pig atria:A role of protein kinase" J.Pharmacol.Exp.Ther.266. 1202-1212 (1993)

Hattori Y.,et al.：“内皮素-1 在豚鼠心房中的双组分正性肌力作用：蛋白激酶的作用”J.Pharmacol.Exp.Ther.266。

Takeda Y., et al.: "Membrane potential dependent effect of dihydropyridin Ca^<2+> channel agonisto on cardiac L-type calcium channels." JPN.J.Electrocardiology. 12. 574 (1992)

Takeda Y.等人：“二氢吡啶Ca^2通道激动剂对心脏L型钙通道的膜电位依赖性作用。”