| Project/Area Number |
16590191
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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 pharmacology
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| Research Institution | Shinshu University |
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Principal Investigator |
YAMADA Mitsuhiko Shinshu University, School of Medicine, Professor, 医学部, 教授 (10263237)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | ATP-sensitive K^+ channels / sulfonylurea receptors / ABC proteins / nucleotide-binding domains / nucleotides / allosteric model / K^+ channel openers / Kir6.2 / クレアチンキナーゼ / 平滑筋 |
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| Research Abstract |
An ATP-sensitive K^+ (K_<ATP>) channel is composed of four sulfonylurea receptors (SUR) and four Kir6.2 subunits. SUR is a member of the ABC protein superfamily and bears 17 transmembrane domains (TMD) and two nucleotide-binding domains (NBD1 and NBD2). K^+ channel openers such as nicorandil activate K_<ATP> channels by binding to the 17^<th> TMD of SUR2. SUR2A and SUR2B differ only in the C-terminal 42 amino acids and have the same TMD and NBDs. Nevertheless, SUR2B/Kir6.2 channels show〜100 times higher sensitivity to nicorandil than SUR2A/Kir6.2 channels.
In this study, we found the followings by using the molecular biological technique, the patch clamp method and the model prediction. (A) When KATP channels are activated in the presence of intracellular nucleotides, NBD1 and NBD2 in the same SUR molecule form a dimer. (B) C42 regulates the dimerization of NBDs, and NBDs of SUR2B more easily form the dimer than those of SUR2A. (C) There is an allosteric interaction between the 17^<th> TMD and NBDs. (D) Therefore, SUR2B/Kir6.2 channels show higher sensitivity to nicorandil than SUR2A/Kir6.2 channels.
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