SCHWARTZ-JAMPEL SYNDROME .2. NA+ CHANNEL DEFECT CAUSES MYOTONIA
SCHWARTZ-JAMPEL SYNDROME .2. NA+ CHANNEL DEFECT CAUSES MYOTONIA
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DOI：
10.1002/mus.880130609
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发表时间：
1990-06-01
期刊：
影响因子：
3.4
通讯作者：
SPAANS, F
中科院分区：
文献类型：
--
作者：
LEHMANNHORN, F;IAIZZO, PA;SPAANS, F
对一例Schwartz-Jampel综合征患者的骨骼肌纤维进行了体外研究。纤维具有正常的静息膜电位，但其静息[Ca 2 +]i升高。静息电位不稳定，自发去极化引起所有纤维的抽搐。刺激收缩的特点是明显减缓松弛，这是由于电后活动。箭毒（0.7 μ M）、妥卡尼（50 μ M）和苯妥英（80 μ M）对肌强直活性都没有影响。相反，普鲁卡因胺（200 μ M）抑制过度兴奋而不影响抽搐幅度。5根纤维的稳态电流-电压关系正常，3根纤维的稳态电流-电压关系改变。这些后者的纤维有一个增加的比膜电阻由于Cl-电导降低。采用细胞贴附式膜片钳模式研究了钠离子通道。在任何类型的纤维上的所有补丁，去极化脉冲引起延迟，同步开放的Na+通道。这些异常的开口甚至发生在表面膜复极化之后。我们假设这些改变的膜电导是负责过度兴奋和相关的松弛减慢。
Skeletal muscle fibers from a patient with Schwartz-Jampel syndrome were studied in vitro. The fibers had normal resting membrane potentials, but their resting [Ca2+]i was elevated. The resting potentials were unstable and spontaneous depolarizations caused twitching in all fibers. Stimulated contractions were characterized by markedly slowed relaxation which was due to electrical after-activity. Neither curare (0.7 .mu.M), tocainide (50 .mu.M), nor phenytoin (80 .mu.M) had an effect on the myotonic activity. In contrast, procainamide (200 .mu.M) suppressed the hyperexcitability without affecting the twitch amplitude. The steady-state current-voltage relation was normal in 5 fibers, but altered in 3 others. These latter fibers had an increased specific membrane resistance owing to a decreased Cl- conductance. The Na+ channels were investigated in the cell-attached patch clamp mode. In all patches on either type of fiber, depolarizing pulses elicited delayed, synchronized openings of Na+ channels. These abnormal openings occurred even after the surface membrane repolarized. We hypothesized that these altered membrane conductances are responsible for the hyperexcitability and the associated slowed relaxation.