Taouis M, Sheldon R S, Duff H J
Department of Medicine, University of Calgary, Alberta, Canada.
J Clin Invest. 1991 Aug;88(2):375-8. doi: 10.1172/JCI115313.
Class I antiarrhythmic drugs inhibit the sodium channel by binding to a drug receptor associated with the channel. In this report we show that in vivo administration of the class I antiarrhythmic drug mexiletine to rats induces sodium channel upregulation in isolated cardiac myocytes. The number of sodium channels was assessed with a radioligand assay using the sodium channel-specific toxin [3H]batrachotoxinin benzoate ([3H]BTXB). The administration of mexiletine to rats induced a dose-dependent increase in [3H]BTXB total specific binding (Bmax) on isolated cardiac myocytes. Sodium channel numbers were 15 +/- 5, 29 +/- 9, and 54 +/- 4 fmol/10(5) cells after 3 d treatment with 0, 50 mg/kg per d, and 150 mg/kg per d mexiletine (P less than 0.001, analysis of variance). Sodium channel number increased monoexponentially to a steady-state value within 3 d with a half-time of increase of 1.0 d. After cessation of treatment with mexiletine the number of sodium channels returned to normal within 12 d. Finally, treatment with mexiletine altered only sodium channel number; the Kd for [3H]BTXB and the IC50 for mexiletine were not different for myocytes prepared from control and mexiletine-treated rats.
I类抗心律失常药物通过与通道相关的药物受体结合来抑制钠通道。在本报告中，我们表明，给大鼠体内施用I类抗心律失常药物美西律可诱导分离的心肌细胞中钠通道上调。使用钠通道特异性毒素[3H]蝙蝠葛毒素苯甲酸酯（[3H]BTXB）的放射性配体测定法评估钠通道的数量。给大鼠施用美西律会导致分离的心肌细胞上[3H]BTXB总特异性结合（Bmax）呈剂量依赖性增加。用0、50mg/kg/天和150mg/kg/天的美西律处理3天后，钠通道数量分别为15±5、29±9和54±4fmol/10(5)个细胞（方差分析，P<0.001）。钠通道数量在3天内呈单指数增加至稳态值，增加的半衰期为1.0天。停止使用美西律治疗后，钠通道数量在12天内恢复正常。最后，美西律治疗仅改变了钠通道数量；从对照大鼠和美西律处理的大鼠制备的心肌细胞中，[3H]BTXB的Kd和美西律的IC50没有差异。
