G-protein dependent kinetics of ionic channels of cardiac pacemaker cells after cold acclimation

冷适应后心脏起搏细胞离子通道的 G 蛋白依赖性动力学

• 批准号: 14570040
• 负责人: MITSUIYE Tamotsu
• 金额: $ 2.24万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570040/
• 关键词: cold stress; cardiac myocytes; G-protein; L-type Ca channels; autonomic regulation; heart rate variability; カルシウムチャネル; 心拍数; 自律神経; 呼吸; 寒冷適応; 心ペースメーカー細胞; G蛋白; 膜電流

Mice were bred in a cold room (15 ℃), and the effects of the cold stress on the L-type Ca channel of cardiac ventricular and pacemaker cells were analyzed. The G-protein dependent slow inactivation kinetics of the L-type Ca channels developed within a week. The slow inactivation in cold acclimated mice was abolished by dialyzing cell with GDP-γS through pipette. However, the slow inactivation was not observed in cells dissociated from mice bred in a warm room (30 ℃) even after the dialysis with GTP-γS These results suggested that small G-proteins may be involved in the slow inactivation. Mice model is profitable for the analysis of the long-term regulation of ionic channels, which is caused by cold stress because the acclimation occurs within a week. Analysis of the autonomic activities by measuring RR-intervals revealed that the rapid cold exposure of mice not only increase the heart rate but also suppress the variation of the beat to beat intervals. Thus it may be suggested that the heart of the cold stressed mice are always exposed to the mechanical stress attributable to the thoracic pressure change by ventilations. To further study the relationship between the respiration and heart rate, I developed a new system for recording and analyzing autonomic regulation of the heart.

将小鼠置于冷室（15 ℃）中饲养，观察冷应激对小鼠心室肌细胞和起搏细胞L型钙通道的影响。L型钙通道的G蛋白依赖性慢失活动力学在一周内发展。用GDP-γS透析细胞可消除冷习服小鼠的慢失活。而在30 ℃温室饲养的小鼠，经GTP-γS透析后，细胞的慢失活仍不明显。提示小G蛋白可能参与慢失活。小鼠冷应激适应期在一周内，因此，该模型有利于研究冷应激对离子通道的长期调节。通过测量RR间期分析自主活动显示，小鼠的快速冷暴露不仅增加心率，而且抑制心跳间隔的变化。提示冷应激小鼠心脏始终处于机械应力作用下，这是由于通气引起的胸压变化所致。为了进一步研究呼吸和心率之间的关系，我开发了一个新的系统来记录和分析心脏的自主调节。

项目成果

Tamotsu Mitsuiye, Akinori Noma: "Inactivation of cardiac Na^+ channel simply through open states as revealed by single-channel analysis in guinea pig ventricular myocytes."Japanese Journal of Physiology. 52. 457-469 (2002)

Tamotsu Mitsuiye、Akinori Noma：“豚鼠心室肌​​细胞的单通道分析显示，心脏 Na^ 通道的失活仅通过开放状态进行。”《日本生理学杂志》。

Mitsuiye, T., Toyoda, F., Morita, T., Noma, A.: "Quantification of autonomic activities underlying heart rate regulation in mice."Japanese Journal of Physiology. 53. S-179 (2003)

Mitsuiye, T.、Toyoda, F.、Morita, T.、Noma, A.：“小鼠心率调节基础自主活动的量化。”日本生理学杂志。

Sarai, N, Kihara, Y., Izumi, T., Mitsuiye, T., Matsuoka, S., Noma, A.: "Nonunifonnity of sarcomere shortnings in the isolated rat ventricular myocyte."The Japanese Journal of Physiology. V. 53,S123,Supplement. (2003)

Sarai，N，Kihara，Y.，Izumi，T.，Mitsuiye，T.，Matsuoka，S.，Noma，A.：“离体大鼠心室肌细胞中肌节缩短的不均匀性。”日本生理学杂志。

Nobuaki Sarai, Yasuki Kihara, Toshiaki Izumi, Tamotsu Mitsuiye, Satoshi Matsuoka, Akinori Noma: "Nonuniformity of sarcomere shortnings in the isolated rat ventricular myocytes."Japanese Journal of Physiology. 52. 371-381 (2002)

Nobuaki Sarai、Yasuki Kihara、Toshiaki Izumi、Tamotsu Mitsuiye、Satoshi Matsuoka、Akinori Noma：“离体大鼠心室肌细胞中肌节缩短的不均匀性。”日本生理学杂志。

Nobuaki Sarai, Yasuki Kihara, Toshiaki Izumi, Tamotsu Mitsuiye, Satoshi Matsuoka, Akinori Noma: "Nonuniformity of Sarcomere Shortenings in the Isolated Rat Ventricular Myocyte."The Japanese Journal of Physiology. 52. 457-469 (2002)

Nobuaki Sarai、Yasuki Kihara、Toshiaki Izumi、Tamotsu Mitsuiye、Satoshi Matsuoka、Akinori Noma：“离体大鼠心室肌细胞肌节缩短的不均匀性。”日本生理学杂志。