Study on the regulation of Na/Ca exchange in isolated cardiac myocytes.

离体心肌细胞Na/Ca交换调控的研究。

• 批准号: 08670778
• 负责人: TERADA Hajime
• 金额: $ 1.47万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670778/
• 关键词: Na^<2+>; Ca^<2+> exchanger,; Ca^+ overload,; Metabolic inhibition,; Arrhythmia; Na; Ca交換機構; Ca過負荷; 不整脈; 強心配糖体; 興奮-収縮連関; 再灌流障害; 代謝阻害; acidosis

Ca^<2+> influx via reverse-mode Na^+/Ca^<2+> exchanger was responsible for the Na^+ withdrawal Ca^<2+> transient (SWCT), which is caused by low Na^+ perfusion in isolated cardiac myocytes. The SWCT was inhibited during metabolic inhibition despite an increase in [Na^+] while it was increased on the washout of metabolic inhibitor. It was suggested that Na^+/Ca^<2+> exchanger was inhibited during metabolic inhibition in spite of an increase in electrical gradient of Na^+.KB-R7943, a specific inhibitor of reverse-mode Na^+ /Ca^<2+> exchanger, did not change the cellular contraction and Ca^<2+> transient in steady-state condition. KB-R7943 also did not change the Ca^<2+> content in the sarcoplasmic reticulum, post-rest potentiation of contraction and Ca^<2+> transient, and the action potential. On the other hand, KB-R7943 inhibited an increase in diastolic [Ca2^<2+>]i and spontaneous Ca^<2+> oscillation in myocytes in which [Na^+]i was increased by strophanthidin while it did not inhibit the positive inotropic effect of strophanthidin. In addition, KB-R7943 reduced the incidence of reoxygenation-induced arrhythmias and facilitated the recovery of contraction after reoxygenation. These results suggested that Ca^<2+> influx via reverse-mode Na^+/Ca^<2+> exchanger dose not have the significant roles in normal excitation-contraction coupling and positive inotropy of cardiac glycoside while it is related to arrhythmogenesis and Ca^<2+> overload in myocytes in which [Na^<2+>]i was elevated by cardiac glycoside and metabolic inhibition.

通过反向Na^+/Ca^2+交换器的Ca^2+内流是Na^+撤回Ca^2+瞬变（SWCT）的原因，SWCT是由分离的心肌细胞中的低Na^+灌注引起的。在代谢抑制期间，尽管[Na^+]增加，SWCT仍受到抑制，而在代谢抑制剂洗脱时，SWCT增加。结果表明，在代谢抑制过程中，尽管Na^+电梯度增加，但Na^+/Ca^2+交换仍受到抑制，而Na^+ /Ca ^2+交换抑制剂KB-R7943在稳态条件下不改变细胞收缩和Ca^2+瞬变。KB-R7943也不改变肌浆网中的Ca^<2+>含量、静息后收缩增强和Ca^<2+>瞬变以及动作电位。另一方面，KB-R7943可抑制毒毛旋花子苷增加心肌细胞[Na^+]i的舒张期[Ca ^2 +]i增加和自发性Ca^2+振荡，但不抑制毒毛旋花子苷的正性肌力作用。此外，KB-R7943降低了复氧诱导的心律失常的发生率，并促进复氧后收缩的恢复。上述结果提示，通过Na^+/Ca^2+交换器的Ca^2+内流在正常的兴奋-收缩偶联和强心苷的正性变力作用中不起重要作用，而与强心苷和代谢抑制引起的[Na^2+]i升高引起的心肌细胞内钙超载和心肌细胞内钙生成有关。

项目成果

Hayashi H, Terada H et al: "Prevention of reoxygenation-induced arrly chmias in guinea pig papillary muscles" J.Cardiovasc.Pharmacol.27. 816-824 (1996)

Hayashi H、Terada H 等人：“预防豚鼠乳头肌中再氧合诱导的 arrly chmias”J.Cardiovasc.Pharmacol.27。

Nakamura T, Hayashi H et al.: "A single all model of myocordial reperfusion injury : changes in intracellular Na^+ and Ca^<2+> concentration" Mol.Cell.Biochem. (in press). (1998)

Nakamura T、Hayashi H 等人：“心肌再灌注损伤的单一全模型：细胞内 Na^2 和 Ca^2 浓度的变化”Mol.Cell.Biochem。

加藤秀樹, 佐藤洋, 寺田肇他: "単離心筋細胞の代謝阻害時における細胞内Na動態とその調節機構" 心筋の構造と代謝. 18. 409-414 (1996)

Hideki Kato、Hiroshi Sato、Hajime Terada 等：“离体心肌细胞代谢抑制过程中的细胞内 Na 动力学及其调节机制”《心肌结构与代谢》18. 409-414 (1996)。

杉山志保,寺田肇 他: "Na^+/H^+交換機構の調節における解糖系及び酸化的リン酸化の役割" 心筋の構造と代謝-1997-. 20(in press). (1998)

Shiho Sugiyama、Hajime Terada 等：“糖酵解和氧化磷酸化在调节 Na^+/H^+ 交换机制中的作用”心肌的结构和代谢-1997-（印刷中）。

Hayashi H,Terada H,McDonald TF.: "Arrhythmia and electrical heterogeneity during prolonged hypoxia in guinea pig papillary muscles." Can.J.Physiol.Pharmacol.75. 44-51 (1997)

Hayashi H、Terada H、McDonald TF.：“豚鼠乳头肌长期缺氧期间的心律失常和电不均匀性。”