Sarcoplasmic Reticulum Ca 2+ Refilling Controls Recovery From Ca 2+ -Induced Ca 2+ Release Refractoriness in Heart Muscle

Circulation Research - Tập 95 Số 8 - Trang 807-813 - 2004
Péter Szentesi1,2,3, Christophe Pignier1,2,3, Marcel Egger1,2,3, Evangelia G. Kranias1,2,3, Ernst Niggli1,2,3
1From the Department of Physiology (P.S., C.P., M.E., E.N.), University of Bern, Bern, Switzerland; the Department of Physiology (P.S.), Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; and the Department of Pharmacology and Cell Biophysics (E.G.K.), University of Cincinnati, Cincinnati, Ohio.
2the Department of Pharmacology and Cell Biophysics (E.G.K.), University of Cincinnati, Cincinnati, Ohio.
3the Department of Physiology (P.S.), Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

Tóm tắt

In cardiac muscle Ca 2+ -induced Ca 2+ release (CICR) from the sarcoplasmic reticulum (SR) is initiated by Ca 2+ influx via L-type Ca 2+ channels. At present, the mechanisms underlying termination of SR Ca 2+ release, which are required to ensure stable excitation-contraction coupling cycles, are not precisely known. However, the same mechanism leading to refractoriness of SR Ca 2+ release could also be responsible for the termination of CICR. To examine the refractoriness of SR Ca 2+ release, we analyzed Na + -Ca 2+ exchange currents reflecting cytosolic Ca 2+ signals induced by UV-laser flash-photolysis of caged Ca 2+ . Pairs of UV flashes were applied at various intervals to examine the time course of recovery from CICR refractoriness. In cardiomyocytes isolated from guinea-pigs and mice, β-adrenergic stimulation with isoproterenol-accelerated recovery from refractoriness by ≈2-fold. Application of cyclopiazonic acid at moderate concentrations (<10 μmol/L) slowed down recovery from refractoriness in a dose-dependent manner. Compared with cells from wild-type littermates, those from phospholamban knockout (PLB-KO) mice exhibited almost 5-fold accelerated recovery from refractoriness. Our results suggest that SR Ca 2+ refilling mediated by the SR Ca 2+ -pump corresponds to the rate-limiting step for recovery from CICR refractoriness. Thus, the Ca 2+ sensitivity of CICR appears to be regulated by SR Ca 2+ content, possibly resulting from a change in the steady-state Ca 2+ sensitivity and in the gating kinetics of the SR Ca 2+ release channels (ryanodine receptors). During Ca 2+ release, the concomitant reduction in Ca 2+ sensitivity of the ryanodine receptors might also underlie Ca 2+ spark termination by deactivation.

Từ khóa


Tài liệu tham khảo

10.1038/415198a

10.1085/jgp.85.2.247

10.1126/science.8235594

10.1016/S0006-3495(92)81615-6

10.1152/ajpcell.1996.270.1.C148

10.1073/pnas.95.25.15096

10.1113/jphysiol.2003.046367

10.1016/S0008-6363(96)00259-3

DelPrincipe F, Egger M, Niggli E. Calcium signalling in cardiac muscle: refractoriness revealed by coherent activation. Nat Cell Biol. 1999; 415: 323–329.

10.1126/science.2173135

10.1161/res.75.3.8062415

Szentesi P, Pignier C, Kranias EG, Egger M, Niggli E. SR Ca determines recovery of CICR from refractoriness in cardiac myocytes. J Muscle Res Cell Motil. 2003; 24: 359.

Egger M, Szentesi P, Pignier C, Kranias EG, Niggli E. SR Ca2+ controls recovery from refractoriness and termination of CICR in cardiac muscle. Biophys J. 2004; 86: 344a.

10.1016/S0006-3495(93)81105-6

10.1113/jphysiol.1989.sp017700

10.1016/S0006-3495(96)79644-3

10.1016/S0014-2999(96)00745-5

Valdivia HH, Kaplan JH, Ellis-Davies GCR, Lederer WJ. Rapid adaptation of cardiac ryanodine receptors: modulation by Mg2+ and phosphorylation. Science. 1995; 31: 1997–2000.

10.1074/jbc.M207028200

10.1038/342090a0

10.1016/S0092-8674(00)80847-8

10.1016/S0021-9258(19)84646-X

10.1111/j.1476-5381.1994.tb17092.x

10.1126/science.8387229

10.1111/j.1469-7793.1998.667bs.x

10.1152/ajpcell.1995.268.5.C1313

10.1073/pnas.1932318100

10.1016/S0006-3495(97)78051-2

10.1152/ajpcell.1990.258.1.C189

10.1016/S0006-3495(00)76596-9

10.1152/ajpcell.1997.272.2.C657

10.1152/ajpheart.1998.274.4.H1335

10.1113/jphysiol.1995.sp020991

10.1016/S0006-3495(02)75149-7

10.1161/01.res.0000032490.04207.bd

10.1007/s004240050233

10.1016/S0006-3495(98)77674-X

10.1074/jbc.M312446200

10.1074/jbc.270.16.9027

10.1016/S0006-3495(04)74271-X

10.1126/science.276.5313.800

10.1161/01.res.0000115944.10681.eb

Thông tin
Thông tin xuất bản

Circulation Research

Tập 95 Số 8

807-813

Thông tin tác giả