| Project/Area Number |
13670743
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Tokai University |
|---|
Principal Investigator |
ISHIDA Hideyuki Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (20222424)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SATO Toshiaki Chiba University, School of Medicine, Assistant Professor, 医学部, 助教授 (60244159)
BAN Kazunobu Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (90256090)
|
|---|
| Project Period (FY) |
2001 – 2003
|
| Project Status |
Completed (Fiscal Year 2003)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Keywords | mitochondria / calcium / ATP / preconditioning / cardioprotection |
|---|
| Research Abstract |
We tested whether opening of mitochondrial ATP-sensitive K^+ (mitoK_<ATP>) channels depolarizes mitochondrial membrane potential (ΔΨ_m), and thereby prevents the mitochondrial Ca^<2+> overload. With the use of Nipkow disk confocal system, the mitochondrial Ca^<2+> concentration ([Ca^<2+>]_m) and ΔΨ_m in rat ventricular myocytes were measured by loading cells with Rhod-2 and JC-1, respectively. Exposure to ouabain (1 mmol/L) for 30 min produced mitochondrial Ca^<2+> overload and the intensity of Rhod-2 fluorescence significantly increased. Treatment of myocytes with the mito_<KAT> channel openers, diazoxide or nicorandil, blunted the ouabain-induced mitochondrial Ca^<2+> overload. Moreover, diazoxide and nicorandil significantly depolarized the ΔΨ_m and reduced the intensity of JC-1 fluorescence during application of ouabain. These effects of diazoxide and nicorandil were blocked by the mitoK_<ATP> channel blocker 5-hydroxydecanoate. These results indicate that opening of mitoK_<ATP> channels prevents a mitochondrial Ca^<2+> overload in association with ΔΨ_m depolarization, and thereby protects myocardium against ischemic damage.
|
