Fluorescent probing with felodipine of the dihydropyridine receptor and its interaction with the ryanodine receptor calcium release channel

被引:6
作者
Minarovic, I [1 ]
Mészaros, LG [1 ]
机构
[1] Med Coll Georgia, Dept Physiol & Endocrinol, Augusta, GA 30912 USA
关键词
excitation-contraction coupling; skeletal muscle; Ca2+ release channel;
D O I
10.1006/bbrc.1998.8233
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The intensity of the fluorescence emission of the fluorescent 1,4-dihydropyridine (DHP) derivative felodipine increased upon binding to both isolated cardiac sarcolemma (SLM) and skeletal muscle sarcoplasmic reticulum (SR) preparations, the latter containing SR-transversal tubule junctional diads and triads. The fluorescence enhancement was due to the binding of felodipine to high-affinity (K-d's Of 0.35 and 1.25 nM in cardiac SLM and skeletal SR, respectively) 1,4-dihydropyridine sites of the dihydropyridine receptor (DHPR), as evidenced in competition experiments with the DHP analog isradipine. In both cardiac SLM, and SR, the felodipine fluiorescence was sensitive to conformational changes of the DHPR, as diltiazem that binds to DHPR at a separate site altered the values of both the K-d and the Hill coefficient characteristic for felodipine binding. In skeletal muscle membranes containing intact TT-SR junctions, ryanodine, a specific ligand of the ryanodine receptor calcium release channel (RyRC), also induced changes in felodipine fluorescence, which was eliminated by detergent and high-salt treatment to solubilize the RyRC. These results suggest that i) felodipine fluorescence is useful to probe conformational changes of the DHPR and ii) coupled conformational changes between the DHPR and the RyRC in skeletal muscle indeed occur and could be monitored by measuring felodipine fluorescence. (C) 1998 Academic Press.
引用
收藏
页码:519 / 524
页数:6
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