| Project/Area Number |
17590188
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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 |
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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) |
YAMAMOTO Shintaro Saga University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (40336110)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Ion channel / Potassium channel / Inward rectifier potassium current / Polyamine / Kir2 / カリウムイオンチャネル |
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| Research Abstract |
The classical strong inward rectifier K+ current plays a pivotal role in polarizing the membranes of excitable cells (cardiac myocytes and skeletal muscle fibers) and nonexcitable cells (e.g. smooth muscle cells, vascular endothelial cells and exocrine cells), and is regulated by voltage-dependent channel block by internal cationic particles, such as polyamines. In this study, we studied the polyamine block of the classical strong inward rectifier K+ channels in the Kir2 family. The new findings are as follows.
( 1 ) The Kir2.1 and Kir2.2 currents are both explained as the sum of those through two conductances that differ in their susceptibility to the spermine block and the outward currents are mediated mostly by the small conductance susceptible to the low-affinity block. The inward rectification of Kir2.2 currents induced by the spermine block was stronger than that of Kir2.1 currents because the fractional conductance susceptible to the low-affinity block is smaller in Kir2.2 than in Kir2.1, and the susceptibility to block is greater in Kir2.2.
( 2 ) Reducing external [K^+] shifted the voltage dependences of both the high-and low-affinity block of Kir2.1 channel in parallel with the shift in the equilibrium potential for K^+.
( 3 ) When Kir2.1 mutants in which the negatively charged residues on the wall of the pore were substituted with corresponding uncharged residues, the mutation within the transmembrane pore made virtually all of the Kir2.1 conductance susceptible only to the low-affinity block, whereas the mutation in the cytoplasmic pore significantly reduced the susceptibility to low-affinity block.
( 4 ) Kir2.1 channel exhibits an internal pH sensitive gating that is different from the mechanism of the block by internal cationic particles.
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