Project/Area Number |
09307001
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General physiology
|
Research Institution | KYOTO UNIVERSITY |
Principal Investigator |
NOMA Akimori Kyoto-U. Dept of Physiology, Professor, 医学研究科, 教授 (00132738)
|
Co-Investigator(Kenkyū-buntansha) |
MATSUOKA Satoshi Kyoto-U. Dept of Physiology, Professor, 医学研究科, 助手 (00263096)
SHINAGAWA Yasuko Kyoto-U. Dept of Physiology, Professor, 医学研究科, 助手 (40093249)
MITSUIYE Tamotsu Kyoto-U. Dept of Physiology, Professor, 医学研究科, 助教授 (40174065)
TAKANO Makoto Kyoto-U. Dept of Physiology, Professor, 医学研究科, 助手 (30236252)
|
Project Period (FY) |
1997 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥18,600,000 (Direct Cost: ¥18,600,000)
Fiscal Year 1999: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1998: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1997: ¥7,900,000 (Direct Cost: ¥7,900,000)
|
Keywords | Cardiac pacemaker / Sino-Aticalnode / Spontaneous action potential / Sustained inward current / 持続性内向電流 / パッチクランプ / イオン電流 |
Research Abstract |
The ionic mechanisms underlying the slow diastolic depolarization in the sino-atrial node of the heart is still a matter of debate. Recently we found a new inward current, which was in fact activated by depolarization to the voltage range of the slow diastolic depolarization (-65〜-40 mV). Since the current showed little inactivation during the depolarizing pulse, we called this current IィイD2stィエD2. We aimed to clarify the nature of IィイD2stィエD2. In this research project, we found the existence of IィイD2stィエD2 in rat sinoatrial node. We developed a new method of isolating the pacemaker cells, and recorded the membrane current by applying the patch clamp method. Rat IィイD2stィエD2 was insensitive to TTX, but was blocked by the classical CaィイD12+ィエD1 antagonists, such as nicardipine, D600 and verapamil. The current is enlarged by the β adrenergic stimulation, and this effect was reversed by applying ACh. In parallel to the whole cell study, we attempted to record the single channel current of IィイD2stィエD2. By applying the cell attached patch recording to the guinea-pig pacemaker cells, we could record a NaィイD1+ィエD1-mediated single channel current, which showed almost the same characteristics as the whole cell IィイD2stィエD2. We are developing a new computer model of the pacemaker by including IィイD2stィエD2.
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