Unno T, Inaba Y, Ohashi H, Komori S
Laboratory of Pharmacology, Department of Veterinary Science, Faculty of Agriculture, Gifu University, Gifu 501-1193, Japan.
Toxicol In Vitro. 2002 Apr;16(2):141-50. doi: 10.1016/s0887-2333(01)00114-x.
The effects of organotin compounds on voltage-dependent, tetrodotoxin (TTX)-resistant Na+ channel current (I(Na)) in single cells isolated from guinea pig dorsal root ganglion were investigated using a whole cell patch clamp technique. Extracellular application of tributyltin (TBT) inhibited I(Na) in a concentration-dependent manner with an IC50 of 7.2 microM. TBT (100 microM), when applied intracellularly, was without effect. Triphenyltin (TPT, 100 microM) and dibutyltin (DBT, 100 microM), applied extracellularly, inhibited I(Na) with an efficacy ranking of TBT>TPT>DBT. Monobutyltin (100 microM), whether applied externally or internally, had little effect on I(Na). TBT (30 microM) significantly prolonged both time to peak and half-decay time of I(Na) and shifted the activation curve of I(Na) in the positive direction without changing the slope. No such effect was produced by TPT (100 microM). The results indicate that organotin compounds inhibit voltage-dependent, TTX-resistant Na+ channel activity and suggest that the inhibitory action may account, at least in part, for their neurotoxic effects.
采用全细胞膜片钳技术，研究了有机锡化合物对从豚鼠背根神经节分离的单个细胞中电压依赖性、河豚毒素（TTX）抗性钠通道电流（I(Na)）的影响。细胞外应用三丁基锡（TBT）以浓度依赖性方式抑制I(Na)，IC50为7.2 microM。细胞内应用TBT（100 microM）则无作用。细胞外应用三苯基锡（TPT，100 microM）和二丁基锡（DBT，100 microM）抑制I(Na)，其效力顺序为TBT>TPT>DBT。单丁基锡（100 microM）无论从细胞外还是细胞内应用，对I(Na)几乎没有影响。TBT（30 microM）显著延长了I(Na)的峰值时间和半衰期，并使I(Na)的激活曲线正向移动，而斜率不变。TPT（100 microM）未产生这种效应。结果表明，有机锡化合物抑制电压依赖性、TTX抗性钠通道活性，提示这种抑制作用可能至少部分解释了它们的神经毒性作用。
