Mechanisms of the increase in heart rate induced by mechanical stretch

机械拉伸引起心率增加的机制

• 批准号: 05454266
• 负责人: TOYAMA Junji
• 金额: $ 3.14万
• 依托单位: Nagoya 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: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454266/
• 关键词: sinoatrial node; spontaneous activity; mechanical stretch; strech-sensitive channels; chloride channels; calcium; sarcoplasmic reticulum; caveolae; ガドリニウム

Ionic mechanisms underlying the enhancement of cardiac pacemaking activity by mechanical stretch was investigated in the isolated rabbit sinoatrial (SA) node. A 5s stretch of 0.2-2.0g was applied to small tissue strips (1.5*3.0mm) of the SA node by using a mechanical stimulator. Cycle length of spontaneous excitation (SPCL) was monitored by recording endocardial surface potential through modified bipolar electrodes with high-gain amplification. Influence of neurotransmitters released from nerve terminals was eliminated by atropine and propranolol. A stretch>0.2g caused a significant shortening of SPCL ; there was a positive correlation between the force and the maximum shortening of SPCL. Treament of the preparation with gadolinium (10muM) or glibenclamide (1muM) did not affect the force-response relationship. The positive chronotropic response to the mechanical stretch>0.5g was reduced significantly by treatment with DNDS (5mM) or SITS (1mM). The positive chronotropic response was also reduced in the low Ca^<2+> (0.36mM) medium, and by bath application of ryanodine (0.1muM) or thapsigargin (2muM). In the electron microscopic examination on the morphology of SA node cells, an increase of caveolae opening in the cell membrane was observed. These findings suggest thah the stretch-induced enhancement of pacemaking activity in the mammalian SA node is mediated in part by stretch-activated C1^- channels and in part by an alteration of Ca^<2+> dynamics.

在离体家兔窦房结上研究了牵张增强心脏起搏活动的离子机制。通过使用机械刺激器将0.2-2.0g的5s拉伸施加到SA结的小组织条（1.5*3.0mm）。自发激发周期长度（SPCL）是通过高增益放大的修饰双极电极记录内皮细胞表面电位来监测的。阿托品和心得安可消除神经末梢释放的神经递质的影响。>0.2g的牵拉力使SPCL显著缩短，牵拉力与SPCL最大缩短量呈正相关。用钆（10 μ M）或格列本脲（1 μ M）处理制剂不影响力-反应关系。DNDS（5 mM）或SITS（1 mM）处理后，对>0.5g的机械牵张的正性变时性反应明显减弱。在低Ca^<2+>（0.36mM）培养基中，以及在水浴中应用ryanodine（0.1 μ M）或thapsigargin（2 μ M），也可降低正性变时性反应。电镜观察SA结细胞的形态，可见细胞膜小窝开口增多。这些发现表明牵张诱导的哺乳动物窦房结起搏活动的增强部分是由牵张激活的C1^-通道介导的，部分是由Ca^2+动力学的改变介导的。

项目成果

Itsuo Kodama, Akiko Arai, and Junji Toyama: "Effects of mechanical stretch on the spontaneous activity of the sino-atrial node." Japanese Journal of Electrocardiology. 1. 18-23 (1994)

Ituo Kodama、Akiko Arai 和 Junji Toyama：“机械拉伸对窦房结自发活动的影响”。

新井章子,児玉逸雄,外山淳治: "機械的伸展に伴う洞結節自動能亢進の機序-外液Ca濃度とL型Caチャネルの関与-" 名古屋大学環境医学研究所年報. 45. 191-193 (1994)

Akiko Arai、Itsuo Kodama、Junji Toyama：“与机械拉伸相关的窦房结自主活动增强的机制 - 外部流体 Ca 浓度和 L 型 Ca 通道的参与 -”名古屋大学环境医学研究所年度报告 45. 191。 -193 (1994)

Akiko Arai, Ryoko Suzuki, Itsuo Kodama and Junji Toyama: "Positive chronotropic effect of mechanical stretch on the sinoatrial node. -Roles of neurotransmitters and stretch activated channels-" Annals of The Research Institute of Environmental Medicine. 4

Akiko Arai、Ryoko Suzuki、Itsuo Kodama 和 Junji Toyama：“机械拉伸对窦房结的正变时作用。-神经递质和拉伸激活通道的作用-”环境医学研究所年鉴。

Akiko Arai, Itsuo Kodama and Junji Toyama: "Effects of mechanical stretch on the pacemaking activity of the isolated rabbit sinoatrial node." Environmental Medicine. 38. 69-72 (1993)

Akiko Arai、Itsuo Kodama 和 Junji Toyama：“机械拉伸对离体兔窦房结起搏活动的影响。”

新井章子、鈴木良子、児玉逸雄、外山淳治: "機械的伸展による洞結節自動能亢進の機序に関する研究" 名古屋大学環境医学研究所年報. 44. 114-116 (1993)

Akiko Arai、Ryoko Suzuki、Itsuo Kodama、Junji Toyama：“机械拉伸增强窦房结自动性的机制研究”名古屋大学环境医学研究所年报 44. 114-116 (1993)。