Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalemic periodic paralysis
Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalemic periodic paralysis
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DOI：
10.1172/jci4552
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发表时间：
1999-03-01
影响因子：
15.9
通讯作者：
Camerino, DC
中科院分区：
文献类型：
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作者：
Tricarico, D;Servidei, S;Camerino, DC
三磷酸腺苷（ATP）敏感性K+（K-ATP）通道是人类和动物骨骼肌纤维中活性最丰富的K+通道。在目前的工作中，我们证明了参与肌肉K-ATP通道的骨骼肌疾病称为低钾型周期性麻痹（HOPP），这是由Ca 2+通道的二氢吡啶受体的突变引起的。从三名携带二氢吡啶受体R528 H突变的HOPP患者中切除的肌肉活检显示肌膜K-ATP电流减少，该电流不受二磷酸腺苷镁（MgADP; 50-100 μ M）的刺激，并被cromakalim部分恢复。与此相反，大的K-ATP电流由MgADP刺激记录在健康受试者。在通道水平上，HOPP患者的K-ATP通道出现异常，呈现多种亚电导状态。在健康受试者中未检测到这些。在体外培养的大鼠肌肉与低K+溶液之间的亚电导状态的K-ATP通道的转换也被观察到。在这些患者中观察到的肌膜K-ATP电流的缺乏解释了该疾病的症状，即，低钾血症、纤维的去极化以及可能的胰岛素施用后的麻痹。
The adenosine triphosphate (ATP)-sensitive K+ (K-ATP) channel is the most abundant K+ channel active in the skeletal muscle fibers of humans and animals. In the present work, we demonstrate the involvement of the muscular K-ATP channel in a skeletal muscle disorder known as hypokalemic periodic paralysis (HOPP), which is caused by mutations of the dihydropyridine receptor of the Ca2+ channel. Muscle biopsies excised from three patients with HOPP carrying the R528H mutation of the dihydropyridine receptor showed a reduced sarcolemma K-ATP current that was not stimulated by magnesium adenosine diphosphate (MgADP; 50-100 mu M) and was partially restored by cromakalim. In contrast, large K-ATP currents stimulated by MgADP were recorded in the healthy subjects. At channel level, an abnormal K-ATP channel showing several subconductance states was detected in the patients with HOPP. None of these were surveyed in the healthy subjects. Transitions of the K-ATP channel between subconductance states were also observed after in vitro incubation of the rat muscle with low-K+ solution. The lack of the sarcolemma K-ATP current observed in these patients explains the symptoms of the disease, i.e., hypokalemia, depolarization of the fibers, and possibly the paralysis following insulin administration.