2000 Fiscal Year Final Research Report Summary
Studies on the regulation of myocardial SR calcium release channel under in situ environment
| Project/Area Number |
11670105
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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 | TOHO UNIVERSITY |
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Principal Investigator |
TANAKA Hikaru Toho University School of Pharmaceutical Sciences Associate Professor, 薬学部, 助教授 (40236617)
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| Project Period (FY) |
1999 – 2000
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| Keywords | mouse myocardium / sarcoplasmic reticulum / calcium ion / cameleon / adenovirus vector / ryanodine receptor |
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| Research Abstract |
cDNAs for Yellow Cameleons with targeting sequences towards the mitochondria and endoplasmic reticulum were packaged into an inproved adenoviral vector and were introduced to primary cultured cardiomyocytes and hepatocytes. The targetting of the probes to organella were confirmed by comparing the fluorescence with those of TMRE etc. Difference in excitation-contraction mechanisms between the atria and ventricle were examined with rapid scanning confocal microscopy. A propagation of CICR mechanisms was involved in normal EC coupling in atrial myocytes but not in ventricular myocytes. This difference was due to the absence of T-tubules in atrial myocytes rather than difference in the properties of individual release unitsand might explain some of the pharmacological difference between the atria and ventricle. We examined the role of three membrane proteins in triggering calcium release from the ryanodine receptor channel. In both atrial and ventricular cardiomyocytes, L-type, but not T-type calcium channels were involved in triggering calcium release. The sodium-calcium exchanger, when activated by factors such as alpha adrenergic stimulation, was found to reduce calcium release from the sarcoplasmic reticulum indirectly through decrease in calcium load.
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