FK506 Alters Sarcoplasmic Reticulum Calcium Release in Neonatal Piglet Cardiac Myocytes
作者:
CHARLENE HOHL,
RUTH ALTSCHULD,
期刊:
Pediatric Research
(OVID Available online 1999)
卷期:
Volume 46,
issue 3
页码: 316-319
ISSN:0031-3998
年代: 1999
出版商: OVID
数据来源: OVID
摘要:
Tacrolimus (FK506) is a potent immunosuppressive drug that, when complexed to a family of immunophilin proteins known as FK binding proteins, inhibits calcineurin in T lymphocytes. Although i.v. use of FK506 in pediatric transplant recipients has been linked to development of cardiomyopathies, its mechanism of cardiotoxicity has not been examined in a neonatal animal model. In our study the effects of FK506 were investigated in cardiac myocytes isolated from newborn piglets. The peak amplitude of electrically triggered fura-2 Ca2+transients was increased in FK506-treated myocytes, but Ca2+transient duration and baseline fura-2 Ca2+ratios were not altered.45Ca2+uptake by digitonin-lysed piglet cells decreased at pCa ≤ 6.0, indicating that sarcoplasmic reticulum efflux channels were leaky. The results suggest that elevated release of sarcoplasmic reticulum Ca2+during systole contributes to cardiotoxic effects observed in children.
返 回