Liu S H, Fu W M, Lin-Shiau S Y
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Eur J Pharmacol. 1993 Jan 26;231(1):23-30. doi: 10.1016/0014-2999(93)90679-c.
The myotonic activity of mouse soleus and extensor digitorum longus muscles induced by either a combination of K+ channel blockers (4-aminopyridine) and a Cl- channel blocker (9-anthracene carboxylic acid) or a Cl- channel blocker in low Ca2+ (0.25 mM) Krebs or a Na+ channel activator (veratridine) was characterized in this paper. Myotonic activity was characterized by an increase in both the contraction amplitude and contraction duration accompanied by stimulus-related repeated action potentials. The slow soleus and fast extensor digitorum longus muscles appeared to differ in their responses to these ion channel modifiers. Nevertheless, chlorpromazine at a low concentration of 1 microM significantly inhibited all kinds of myotonic activity; it reduced the prolonged contraction duration and attenuated the stimulus-related repeated action potential firing. This depressant action of chlorpromazine was apparently not correlated with inhibition of either calmodulin or phospholipase A2 activity, since the myotonic depressant action of calmodulin inhibitors, such as dibucaine, flunarizine, chlorpromazine, trifluoperazine and diltiazem, was unrelated to their potency in inhibiting the activity of calmodulin or phospholipase A2. However, phosphatidylcholine was found to inhibit the myotonic depressant action of chlorpromazine. It is therefore, tentatively concluded that chlorpromazine interacted with membrane phospholipids, thereby changing membrane ion channel activity and depressing myotonic activity. These findings indicate that chlorpromazine might be useful in the management of clinical myotonia.
本文对钾通道阻滞剂（4-氨基吡啶）和氯通道阻滞剂（9-蒽甲酸）联合使用、低钙（0.25 mM）Krebs液中的氯通道阻滞剂或钠通道激活剂（藜芦碱）诱导的小鼠比目鱼肌和趾长伸肌的强直性活动进行了表征。强直性活动的特征是收缩幅度和收缩持续时间增加，并伴有与刺激相关的重复动作电位。慢肌比目鱼肌和快肌趾长伸肌对这些离子通道调节剂的反应似乎有所不同。然而，低浓度1 microM的氯丙嗪显著抑制了所有类型的强直性活动；它缩短了延长的收缩持续时间，并减弱了与刺激相关的重复动作电位发放。氯丙嗪的这种抑制作用显然与钙调蛋白或磷脂酶A2活性的抑制无关，因为钙调蛋白抑制剂如丁卡因、氟桂利嗪、氯丙嗪、三氟拉嗪和地尔硫卓的强直性抑制作用与其抑制钙调蛋白或磷脂酶A2活性的效力无关。然而，发现磷脂酰胆碱可抑制氯丙嗪的强直性抑制作用。因此，初步得出结论，氯丙嗪与膜磷脂相互作用，从而改变膜离子通道活性并抑制强直性活动。这些发现表明氯丙嗪可能对临床强直性肌病的治疗有用。
