| Project/Area Number |
15590187
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Saga University (2004)
佐賀医科大学 (2003) |
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Principal Investigator |
YANAGI Keiko Saga University, Faculty of Medicine, Associate professor, 医学部, 助教授 (70265990)
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| Co-Investigator(Kenkyū-buntansha) |
EHARA Tsuguhisa Saga University, Faculty of Medicine, Professor, 医学部, 教授 (50037446)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | cardiac myocyte / ion channel / potassium channel / inward rectifier potassium current / magnesium ion / polyamine / Kir2.1 / potassium current / 心筋 / カリウム電流 / イオン電流 / 内向き整流カリウムチャネル / コンピューターモデル |
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| Research Abstract |
1.The amplitude of the currents through the cardiac strong inward rectifier potassium (K^+) channels is known to be regulated by a voltage-dependent blockade of the channels by intracellular polyamines and Mg^<2+>. However, the detailed mechanism of the blockade is complicated, and is not well understood. We expressed Kir2.1,which is the major subunit of the cardiac inward rectifier K^+ channels, in human embryonic kidney cells 293T and studied the polyamine and Mg^<2+> blockades of the Kir2.1 channel currents recorded from inside-out patch membranes using the voltage-clamp method. We found that the Kir2.1 currents recorded in the presence of various concentrations of cytoplasmic polyamines and Mg^<2+> can be all well described as those flowing through two populations of Kir2.1 channels having different sensitivities to the blockades by polyamines and Mg^<2+>. The relative size of the two populations was slightly altered by an interaction of polyamines with the channel at an intracellu
… More
lar regulatory site. Our results suggested that the outward currents through the cardiac inward rectifier K^+ channels flow mostly through a small population (〜10%) of the channels having lower sensitivity to cytoplasmic blockers. Physiological concentrations of intracellular Mg^<2+> blocks a major population (〜90%) of the channels showing higher sensitivity to cytoplasmic blockers and thereby increases the amplitude of the outward currents in the presence of polyamines.
2.We studied the mechanisms underlying the difference between the strong inward rectifier K^+ currents in the cardiac atrial and ventricular myocytes. Our results indicated that the difference in the subunits (Kir2.1,Kir2.2,or Kir2.3) composing the channel cannot explain the difference, but a higher concentration of intracellular polyamines can change the currents flowing through the Kir2.1 channels from a ‘ventricular type' to an ‘atrial type'. The total and free polyamine concentrations measured were indeed higher in the atrial tissues of the guinea-pig hearts. Less
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