Mounsey J P, Xu P, John J E, Horne L T, Gilbert J, Roses A D, Moorman J R
Department of Internal Medicine (Cardiovascular Division), University of Virginia Health Sciences Center, Charlottesville 22908, USA.
J Clin Invest. 1995 May;95(5):2379-84. doi: 10.1172/JCI117931.
In myotonic muscular dystrophy, abnormal muscle Na currents underlie myotonic discharges. Since the myotonic muscular dystrophy gene encodes a product, human myotonin protein kinase, with structural similarity to protein kinases, we tested the idea that human myotonin protein kinase modulates skeletal muscle Na channels. Coexpression of human myotonin protein kinase with rat skeletal muscle Na channels in Xenopus oocytes reduced the amplitude of Na currents and accelerated current decay. The effect required the presence of a potential phosphorylation site in the inactivation mechanism of the channel. The mutation responsible for human disease, trinucleotide repeats in the 3' untranslated region, did not prevent the effect. The consequence of an abnormal amount of the kinase would be altered muscle cell excitability, consistent with the clinical finding of myotonia in myotonic dystrophy.
在强直性肌营养不良中，异常的肌肉钠电流是强直性放电的基础。由于强直性肌营养不良基因编码一种产物，即人类肌强直性蛋白激酶，其结构与蛋白激酶相似，我们测试了人类肌强直性蛋白激酶调节骨骼肌钠通道的想法。在非洲爪蟾卵母细胞中，人类肌强直性蛋白激酶与大鼠骨骼肌钠通道共表达可降低钠电流幅度并加速电流衰减。该效应需要通道失活机制中存在一个潜在的磷酸化位点。导致人类疾病的突变，即3'非翻译区的三核苷酸重复，并不妨碍这种效应。激酶数量异常的后果将是肌肉细胞兴奋性改变，这与强直性肌营养不良中肌强直的临床发现一致。
