van Lunteren Erik, Sankey Christopher, Moyer Michelle, Snajdar Rudolf M
Department of Medicine (Pulmonary Division), Louis Stokes Cleveland VA Medical Center, Case Western Reserve University, 10701 East Boulevard, Cleveland OH 44106, USA.
J Muscle Res Cell Motil. 2002;23(3):197-204. doi: 10.1023/a:1020967106084.
Migration of myoblasts is an important component of the reparative response to muscle injury, and furthermore may be a key determinant of the success of myoblast transplantation for the treatment of genetic muscle diseases. The present study examined the hypothesis that K+ channels modulate myoblast migration. The migration of cultured L-6 myoblasts was assessed in vitro on confluent cultures with the razor wound method, in the absence and presence of the following agents: 3,4-diaminopyridine and tetraethylammonium (which block several types of K+ channels), apamin and charybdotoxin (which block Ca++-activated K+ channels), glibenclamide (which blocks ATP-sensitive K+ channels), and alpha-, beta-, gamma-, and delta-dendrotoxin (which block voltage-gated K+ channels). Migration was assessed with respect to number of migrated cells, average distance migrated, and total distance migrated. Overall, myoblast migration was stimulated in response to low concentrations of tetraethylammonium, apamin, glibenclamide, and alpha-, beta- and delta-dendrotoxin. With these agents, the number of migrated cells increased by 28-47%, the average distance migrated increased by 22-35%, and the total distance migrated increased by 60-85%. Conversely, migration was inhibited by high concentrations of 3,4-diaminopyridine, tetraethylammonium, and all dendrotoxins. These data indicate that in L-6 myoblasts migration is regulated by K+ channels, and that several types of K+ channels appear to participate in cell migration.
成肌细胞迁移是肌肉损伤修复反应的重要组成部分,此外,它可能是成肌细胞移植治疗遗传性肌肉疾病成功与否的关键决定因素。本研究检验了钾通道调节成肌细胞迁移这一假说。采用刮伤法在体外对汇合培养的L-6成肌细胞进行评估,在有无以下试剂的情况下观察其迁移情况:3,4-二氨基吡啶和四乙铵(可阻断几种类型的钾通道)、蜂毒明肽和蝎毒素(可阻断钙激活钾通道)、格列本脲(可阻断ATP敏感性钾通道)以及α-、β-、γ-和δ-树突毒素(可阻断电压门控钾通道)。从迁移细胞数量、平均迁移距离和总迁移距离方面评估迁移情况。总体而言,低浓度的四乙铵、蜂毒明肽、格列本脲以及α-、β-和δ-树突毒素可刺激成肌细胞迁移。使用这些试剂时,迁移细胞数量增加了28% - 47%,平均迁移距离增加了22% - 35%,总迁移距离增加了60% - 85%。相反,高浓度的3,4-二氨基吡啶、四乙铵以及所有树突毒素均抑制迁移。这些数据表明,在L-6成肌细胞中,迁移受钾通道调节,并且几种类型的钾通道似乎都参与了细胞迁移。