| Project/Area Number |
09670103
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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 | SAITAMA MEDICAL SCHOOL |
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Principal Investigator |
ENDO Makoto Pharmacology, SAITAMA MEDICAL SCHOOL, Professor, 医学部, 教授 (50009990)
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| Co-Investigator(Kenkyū-buntansha) |
IKEMOTO Takaaki Pharmacology, SAITAMA MEDICAL SCHOOL, Reseach Associate, 医学部, 助手 (30275854)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | cardiac muscle / CaィイD12+ィエD1 -induced CaィイD12+ィエD1 release (CICR) / adenine / caffeine / excitation-contraction coupling / CaィイD12+ィエD1 / procaine / sarcoplasmic reticulum / Ca^<2+>によるCa^<2+>放出(CICR) / 筋小胞体 / スキンドファイバー / リアノジン受容体 / Ca^<2+>放出チャネル |
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| Research Abstract |
It is generally believed that physiological contraction of mammalian cardiac muscle is mediated by CaィイD12+ィエD1 released from the sarcoplasmic reticulum (SR) by activation of CaィイD12+ィエD1 -induced CaィイD12+ィエD1 release mechanism (CICR) evoked by CaィイD12+ィエD1 entered from external medium during action potentials. However, since inhibitors of CICR appeared not to inhibit cardiac contraction in our preliminary studies, we examined this problem closely.
We obtained the following results.
1) In the presence of ATP, adenine inhibited CICR also in cardiac muscle as previously shown in Skeletal muscle.
2) Adenine up to 10 mM did not inhibit at all electrically evoked cardiac contraction, but only potentiated it slowly.
3) Adenine initially decreased but then slowly increased action potential-evoked CaィイD12+ィエD1 transient. Conversely on washing adenine CaィイD12+ィエD1 transient initially increased and then decreased to the original level.
4) Procaine inhibited K-induced contraction of cardiac muscle.
The results 1) & 2) appears to indicate that cardiac contraction is not mediated by CICR, but the immediate effect of adenine on CaィイD12+ィエD1 transient and the result 4) clearly support the CICR theory. The apparent discrepancy may be explained by other effects of adenine, inhibition of CaィイD12+ィエD1 uptake by SR and increase of CaィイD12+ィエD1 sensitivity of the contractile system.
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