| Project/Area Number |
08670826
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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 |
Circulatory organs internal medicine
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| Research Institution | Jikei University, School of Medicine |
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Principal Investigator |
MCHIZUKI Seibu JIKEI UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF MEDICINE 4 PROFESSOR, 医学部, 教授 (20130205)
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| Co-Investigator(Kenkyū-buntansha) |
SEKI Shingo LECTURER, 医学部, 講師 (70179323)
TANIGUCHI Masayuki LECTURER, 医学部, 講師 (70179844)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | ATP sensitive K^+ channel / calcium / fura-2 / ischemia / sodium calcium exhanger / ATP sensitive K+channel / furaー2 / anoxia |
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| Research Abstract |
OBJECTIVE : We investigated the roles of ATP sensitive K^+ channel (K_<ATP>) and Na^+/Ca^<2+> exchanger in intracellular Ca^<2+> regulation.
METHODS : Single enzymatically isolated guinea pig ventricular myocytes were exposed to chemical hypoxia with glucose-free Tyrode solution containing 1mM sodium dithionite and were reoxygenated. Intracellular Ca^<2+> concentration ([Ca^<2+>]i) was measured ratiometrically using fura-2 with simultaneous measurement of cell length. Isolated hearts from Sprague-Dawley rats were retrogradely perfused and [Ca^<2+>]i was monitored using fura-2. Ischemia was induced by reduction of flow to 10% of control with electrical pacing.
RESULTS : Hypoxia produced a decrease in Ca^<2+> transient amplitude and an increase in resting [Ca^<2+>]i. K_<ATP> operner accelerated the shortening of action potential duration and suppressed the hypoxic increase in resting [Ca^<2+>]i. The increase in [Ca^<2+>]i induced by Na^+-free exposure was inhibited during hypoxia.
Ischemia also produced an increase in diastolic [Ca^<2+>]i. Treatment of reverse mode Na^+/Ca^<2+> exchanger blocker attenuated the increase in diastolic [Ca^<2+>]i during sustained ischemia and accelerated normalization of [Ca^<2+>] i after reperfusion.
CONCLUSIONS : Both K_<ATP> and Na^+/Ca^<2+> exchanger were importantly involved in intracellular Ca^<2+> regulation during ischemia and reperfusion.
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