Reinvestigation of calcium release mechanism from the sarcoplasmic reticulum in cardiac excitation-contraction coupling.

重新研究心脏兴奋-收缩耦合中肌浆网的钙释放机制。

• 批准号: 09670103
• 负责人: ENDO Makoto
• 金额: $ 2.3万
• 依托单位: SAITAMA MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670103/
• 关键词: cardiac muscle; CaィイD12+ィエD1 -induced CaィイD12+ィエD1 release (CICR); adenine; caffeine; excitation-contraction coupling; CaィイD12+ィエD1; procaine; sarcoplasmic reticulum; Ca^<2+>によるCa^<2+>放出(CICR); 筋小胞体; スキンドファイバー; リアノジン受容体; Ca^<2+>放出チャネル

It is generally believed that physiological contraction of mammalian cardiac muscle is mediated by CaィイD12+ィエD1 released from the sarcoplasmic reticulum (SR) by activation of CaィイD12+ィエD1 -induced CaィイD12+ィエD1 release mechanism (CICR) evoked by CaィイD12+ィエD1 entered from external medium during action potentials. However, since inhibitors of CICR appeared not to inhibit cardiac contraction in our preliminary studies, we examined this problem closely.We obtained the following results.1) In the presence of ATP, adenine inhibited CICR also in cardiac muscle as previously shown in Skeletal muscle.2) Adenine up to 10 mM did not inhibit at all electrically evoked cardiac contraction, but only potentiated it slowly.3) Adenine initially decreased but then slowly increased action potential-evoked CaィイD12+ィエD1 transient. Conversely on washing adenine CaィイD12+ィエD1 transient initially increased and then decreased to the original level.4) Procaine inhibited K-induced contraction of cardiac muscle.The results 1) & 2) appears to indicate that cardiac contraction is not mediated by CICR, but the immediate effect of adenine on CaィイD12+ィエD1 transient and the result 4) clearly support the CICR theory. The apparent discrepancy may be explained by other effects of adenine, inhibition of CaィイD12+ィエD1 uptake by SR and increase of CaィイD12+ィエD1 sensitivity of the contractile system.

一般认为，哺乳动物心肌的生理性收缩是由肌浆网（SR）释放的Ca ~（2+）D_1介导的，其通过激活Ca ~（2+）D_1 D然而，由于CICR抑制剂在我们的初步研究中似乎不抑制心脏收缩，我们仔细研究了这个问题。我们获得了以下结果：1）在ATP存在下，腺嘌呤也抑制心肌中的CICR，如先前在Skeleton肌中所示。2）高达10 mM的腺嘌呤根本不抑制电诱发的心脏收缩，3）腺嘌呤先降低动作电位诱发的Ca ~（2+）D_1_2 + Ca ~（2+）D_1瞬变，然后缓慢增加。腺嘌呤对Ca 2 + D12+ D1瞬变的直接影响（1）和（2）表明，Ca 2 + D12 + D1瞬变不受CICR介导，而腺嘌呤对Ca 2 + D12+ D1瞬变的直接影响（4）支持CICR理论。这种明显的差异可能与腺嘌呤的其他作用、抑制SR摄取Ca ~（2+）D_（12）+Ca ~（2+）D_1和增加收缩系统对Ca ~（2+）D_（12+）D_1的敏感性有关。

项目成果

Ebashi, s., Endou, M. & Ohtsuki, I(分担執筆): "Calcium as a Cellular Requlator (ed. Carafoli & Klee)"Oxford Univ. Press. 642 (1999)

Ebashi, S.、Endou, M. 和 Ohtsuki, I（撰稿人）：“钙作为细胞调节剂（Carafoli 和 Klee 编）”牛津大学出版社 642（1999 年）。

Y.Li, T.Ikemoto, M.Endo: "The disparity between the effect of adenine on cardiac excitation-contraction coupling and that on the calcium-induced calcium release mechanism" Naunyn-Schmiedeberg's Archives of Pharmacology. 358(Suppl2). R685 (1998)

Y.Li、T.Ikemoto、M.Endo：“腺嘌呤对心脏兴奋-收缩耦合的影响与对钙诱导的钙释放机制的影响之间的差异”Naunyn-Schmiedeberg 的药理学档案。