Inhibitory effects of organotin compounds on voltage-dependent, tetrodotoxin-resistant Na + channel current in guinea pig dorsal root ganglion cells

Abstract

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 IC 50 of 7.2 μ m. TBT (100 μ m), when applied intracellularly, was without effect. Triphenyltin (TPT, 100 μ m) and dibutyltin (DBT, 100 μ m), applied extracellularly, inhibited I Na with an efficacy ranking of TBT>TPT>DBT. Monobutyltin (100 μ m), whether applied externally or internally, had little effect on I Na. TBT (30 μ m) 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 μ m). 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.