Potentiation of Ca <sup>2+</sup> Release by cADP-Ribose in the Heart Is Mediated by Enhanced SR Ca <sup>2+</sup> Uptake Into the Sarcoplasmic Reticulum

Circulation Research - Tập 89 Số 7 - Trang 614-622 - 2001
Valeriy Lukyanenko1, Inna Györke2, Theodore F. Wiesner3, Sándor Györke2
1Valeriy Lukyanenko From the Department of Physiology (V.L., I.G., S.G.), Texas Tech University Health Sciences Center, and the Department of Chemical Engineering (T.F.W.), Texas Tech University, Lubbock.
2From the Department of Physiology (V.L., I.G., S.G.), Texas Tech University Health Sciences Center, and the Department of Chemical Engineering (T.F.W.), Texas Tech University, Lubbock.
3Theodore F. Wiesner From the Department of Physiology (V.L., I.G., S.G.), Texas Tech University Health Sciences Center, and the Department of Chemical Engineering (T.F.W.), Texas Tech University, Lubbock.

Tóm tắt

Abstract— cADP-Ribose (cADPR) is a novel endogenous messenger that is believed to mobilize Ca 2+ from ryanodine-sensitive Ca 2+ stores. Despite intense research, the precise mechanism of action of cADPR remains uncertain, and experimental findings are contradictory. To elucidate the mechanism of cADPR action, we performed confocal Ca 2+ imaging in saponin-permeabilized rat ventricular myocytes. Exposure of the cells to cADPR resulted in a slow (>2 minutes) and steady increase in the frequency of Ca 2+ sparks. These effects on local release events were accompanied by a significant increase in sarcoplasmic reticulum (SR) Ca 2+ content. In comparison, sensitization of ryanodine receptors (RyRs) by caffeine, a true RyR agonist, caused a rapid (<1 second) and transient potentiation of Ca 2+ sparks followed by a decrease in SR Ca 2+ content. When the increase in the SR load was prevented by partial inhibition of the SR Ca 2+ with thapsigargin, cADPR failed to produce any increase in sparking activity. cADPR had no significant impact on activity of single cardiac RyRs incorporated into lipid bilayers. However, it caused a significant increase in the rate of Ca 2+ uptake by cardiac SR microsomes. Our results suggest that the primary target of cADPR is the SR Ca 2+ uptake mechanism. Potentiation of Ca 2+ release by cADPR is mediated by increased accumulation of Ca 2+ in the SR and subsequent luminal Ca 2+ -dependent activation of RyRs.

Từ khóa


Tài liệu tham khảo

Bers DM. Excitation-Contraction Coupling and Cardiac Contractile Force. Dordrecht the Netherlands: Kluwer Academic Publishers; 1991.

10.1161/res.85.9.770

10.1152/ajpcell.1994.266.6.C1485

10.1146/annurev.pharmtox.41.1.317

10.1038/364076a0

10.1016/0014-5793(94)00931-7

10.1161/res.75.3.8062431

10.1016/S0960-9822(02)00643-7

10.1074/jbc.274.25.17820

10.1161/res.81.5.879

10.1042/bj3420269

10.1152/ajpheart.2000.279.4.H1482

10.1161/res.79.1.147

10.1111/j.1469-7793.1999.00575.x

Györke S, Lukyanenko V, Györke I. Dual effects of tetracaine on spontaneous calcium release in rat ventricular myocytes. J Physiol (Lond). 1997; 500: 2297–2309.

10.1016/S0006-3495(00)76381-8

10.1016/S0006-3495(01)75741-4

10.1016/S0006-3495(98)77723-9

10.1016/0167-4889(93)90199-Y

10.1152/ajpcell.1996.270.1.C148

10.1007/s004240050233

10.1111/j.1469-7793.1997.665ba.x

10.1016/S0006-3495(97)78184-0

10.1161/res.87.3.201

10.1016/S0008-6363(98)00062-5

10.1152/ajpheart.2001.280.1.H208

10.1113/jphysiol.1991.sp018481

10.1161/res.87.12.1087

10.1152/ajpheart.1998.274.5.H1800

10.1113/jphysiol.1996.sp021708

10.1111/j.1469-7793.1997.021bi.x

Deleted in proof.

10.1016/S0006-3495(95)80378-4

Kobayashi M, Shoji N, Ohizumi Y. Gingerol, a novel cardiotonic agent, activates the Ca2+-pumping ATPase in skeletal and cardiac sarcoplasmic reticulum. Biochim Biophys Acta. 1987; 903: 196–102.

10.1111/j.1432-1033.1997.t01-1-00801.x

10.1016/S0021-9258(19)84754-3

10.1152/physrev.1998.78.4.921

Thông tin
Thông tin xuất bản

Circulation Research

Tập 89 Số 7

614-622

Thông tin tác giả