Inhibitory effects of organotin compounds on voltage-dependent, tetrodotoxin-resistant Na+ channel current in guinea pig dorsal root ganglion cells.
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.
Unno
T
T
Laboratory of Pharmacology, Department of Veterinary Science, Faculty of Agriculture, Gifu University, Gifu 501-1193, Japan.
Inaba
Y
Y
Ohashi
H
H
Komori
S
S
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009947:Organotin Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D009947:Organotin Compounds; D015222:Sodium Channels; D014220:Trialkyltin Compounds; C056189:di-n-butyltin; D013779:Tetrodotoxin; C011559:tributyltin