Effects of a domain peptide of the ryanodine receptor on Ca2+ release in skinned skeletal muscle fibers

American Journal of Physiology - Cell Physiology - Tập 281 Số 1 - Trang C207-C214 - 2001
Graham D. Lamb1, Giuseppe S. Posterino1, Takeshi Yamamoto2, Noriaki Ikemoto2
1Department of Zoology, La Trobe University, Bundoora, Victoria 3086, Australia; and
2Boston Biomedical Research Institute Watertown, Massachusetts 02472

Tóm tắt

Mutations in the central domain of the skeletal muscle ryanodine receptor (RyR) cause malignant hyperthermia (MH). A synthetic peptide (DP4) in this domain (Leu-2442–Pro-2477) produces enhanced ryanodine binding and sensitized Ca2+ release in isolated sarcoplasmic reticulum, similar to the properties in MH, possibly because the peptide disrupts the normal interdomain interactions that stabilize the closed state of the RyR (Yamamoto T, El-Hayek R, and Ikemoto N. J Biol Chem 275: 11618–11625, 2000). Here, DP4 was applied to mechanically skinned fibers of rat muscle that had the normal excitation-contraction coupling mechanism still functional to determine whether muscle fiber responsiveness was enhanced. DP4 (100 μM) substantially potentiated the Ca2+release and force response to caffeine (8 mM) and to low [Mg2+] (0.2 mM) in every fiber examined, with no significant effect on the properties of the contractile apparatus. DP4 also potentiated the response to submaximal depolarization of the transverse tubular system by ionic substitution. Importantly, DP4 did not significantly alter the size of the twitch response elicited by action potential stimulation. These results support the proposal that DP4 causes an MH-like aberration in RyR function and are consistent with the voltage sensor triggering Ca2+ release by destabilizing the closed state of the RyRs.

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Tài liệu tham khảo

10.1074/jbc.272.44.27582

10.1111/j.1469-7793.1998.551bn.x

10.1111/j.1469-7793.2000.t01-1-00507.x

10.1016/S0006-3495(00)76290-4

10.1152/ajpcell.1995.268.6.C1381

10.1016/S0070-2161(08)60768-6

10.1016/S0006-3495(90)82563-7

10.1152/ajpcell.1988.254.1.C107

10.1007/BF00585622

10.1085/jgp.102.2.333

10.1002/(SICI)1097-4598(200001)23:1<4::AID-MUS3>3.0.CO;2-D

10.1046/j.1440-1681.2000.03224.x

10.1111/j.1469-7793.1999.0815n.x

10.1111/j.1469-7793.2001.0715h.x

10.1152/ajpcell.2000.279.4.C891

10.1113/jphysiol.1990.sp018037

10.1113/jphysiol.1991.sp018483

10.1113/jphysiol.1994.sp020253

10.1007/s002329900202

10.1016/S0006-3495(97)78222-5

10.1086/301748

10.1021/bi00349a033

10.1074/jbc.272.3.1628

10.1085/jgp.113.2.177

10.1016/0304-4157(94)00014-5

10.1152/physrev.1996.76.2.537

10.1113/jphysiol.1997.sp021884

10.1152/ajpcell.1997.272.1.C203

10.1085/jgp.106.2.259

10.1111/j.1469-7793.1997.289bn.x

10.1007/BF03257390

10.1111/j.1469-7793.2000.t01-2-00131.x

10.1074/jbc.272.8.5256

10.1152/physrev.1991.71.3.849

10.1111/j.1469-7793.1998.377be.x

10.1113/jphysiol.1981.sp013825

10.1085/jgp.86.6.813

10.1111/j.1469-7793.2000.00447.x

10.1038/336134a0

10.1074/jbc.272.42.26332

10.1152/ajpcell.1991.261.2.C237

10.1074/jbc.275.16.11618

10.1074/jbc.270.34.19936

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American Journal of Physiology - Cell Physiology

Tập 281 Số 1

C207-C214

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