Owen V J, Taske N L, Lamb G D
School of Zoology, La Trobe University, Bundoora, Victoria, Australia.
Am J Physiol. 1997 Jan;272(1 Pt 1):C203-11. doi: 10.1152/ajpcell.1997.272.1.C203.
The inhibitory effect of myoplasmic Mg2+ on Ca2+ release from the sarcoplasmic reticulum (SR) was examined in mechanically skinned skeletal muscle fibers from pigs of different ryanodine-receptor (RyR) genotypes. In fibers from pigs homozygous for the normal RyR allele, the free Mg2+ concentration ([Mg2+]) had to be lowered from the normal resting level of 1 to approximately 0.1 mM to induce Ca2+ release and a force response. Fibers from pigs heterozygous or homozygous for the RyR allele associated with malignant hyperthermia (MH) needed only a smaller reduction in free [Mg2+] to induce Ca2+ release (reduction to 0.1-0.2 and > or = 0.2 mM, respectively). Dantrolene (20 microM) counteracted the effect of this reduced Mg2+ inhibition in MH muscle. The response of muscle fiber bundles to the caffeine-halothane contracture test in the three genotypes correlated well with the responsiveness of single fibers to reduced [Mg2+]. Thus the abnormal responsiveness of MH muscle to various stimuli may largely result from the reduced ability of myoplasmic Mg2+ to inhibit Ca2+ release from the SR.
在来自不同兰尼碱受体(RyR)基因型猪的机械去表皮骨骼肌纤维中,研究了肌质中Mg2+对肌浆网(SR)释放Ca2+的抑制作用。在正常RyR等位基因纯合子猪的纤维中,游离Mg2+浓度([Mg2+])必须从正常静息水平1 mM降至约0.1 mM才能诱导Ca2+释放和产生力反应。来自与恶性高热(MH)相关的RyR等位基因杂合子或纯合子猪的纤维,只需将游离[Mg2+]较小程度降低就能诱导Ca2+释放(分别降至0.1 - 0.2 mM和≥0.2 mM)。丹曲林(20 μM)可抵消这种Mg2+抑制作用降低对MH肌肉的影响。三种基因型的肌纤维束对咖啡因 - 氟烷挛缩试验的反应与单根纤维对降低[Mg2+]的反应性密切相关。因此,MH肌肉对各种刺激的异常反应性可能很大程度上是由于肌质中Mg2+抑制SR释放Ca2+的能力降低所致。