期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1994
卷号：91
期号：25
页码：11953-11957
DOI：10.1073/pnas.91.25.11953
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A soluble 12-kDa FK506 binding protein (FKBP12), the cellular receptor of the immunosuppressive drug FK506, is tightly associated with the Ca2+ release channel of rabbit skeletal muscle sarcoplasmic reticulum [Jayaraman, T., Brillantes, A. M., Timerman, A. P., Fleischer, S., Erdjument-Bromage, H., Tempst, P. & Marks, A. (1992) J. Biol. Chem. 267, 9474-9477]. We have assessed the role of excess free FKBP12 in the function of single Ca2+ release channels incorporated into planar lipid bilayers. The addition of human recombinant FKBP12 (hFKBP12) to the cytoplasmic face of the Ca2+ release channel blocked the flow of cytoplasmic to luminal current (outward current) in a concentration-dependent manner but had no significant effect on the flow of luminal to cytoplasmic current (inward current). The luminal to cytoplasmic flow of current was modulated by Ca2+, Mg2+, ATP, caffeine, and ryanodine in the presence and absence of FKBP12. An immunosuppressive drug, L-683,590, an analog of FK506, did not block or reverse the asymmetrical hFKBP12 blockade of single Ca2+ release channels in planar lipid bilayers. FKBP12 may play a role in regulation of the flow of ions into the lumen of the sarcoplasmic reticulum through the Ca2+ release channel.
