Modulation of tetrodotoxin-resistant sodium channels by dihydropyrazole insecticide RH-3421 in rat dorsal root ganglion neurons.
The effects of the dihydropyrazole insecticide RH-3421 on the retrodotoxin-resistant (TTX-R) voltage-gated sodium channels in rat dorsal root ganglion (DRG) neurons were studied using the whole-cell patch clamp technique. RH-3421 at 10 nM to 1 microM completely blocked action potentials. The sodium currents were irreversibly suppressed by 1 microM RH-3421 in a time- and a dose-dependent manner and the IC50 value of RH-3421 was estimated to be 0.7 microM after 10 min of application. RH-3421 blocked the sodium currents to the same extent over the entire range of test potentials. The sodium conductance-voltage curve was not shifted along the voltage axis by 1 microM RH-3421 application In contrast, both fast and slow steady-state sodium channel inactivation curves were shifted in the hyperpolarizing direction in the presence of 1 microM RH-3421. It was concluded that RH-3421 bound to the resting and inactivated sodium channels to cause block with a higher affinity for the latter state.
Tsurubuchi
Y
Y
Institute of Agriculture and Forestry, University of Tsukuba, Japan.
Zhao
X
X
Nagata
K
K
Kono
Y
Y
Nishimura
K
K
Yeh
J Z
JZ
Narahashi
T
T
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D004351:Drug Resistance; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010477:Perfusion; D010671:Phenylurea Compounds / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000633:toxicity*
D007306:Insecticides; D010671:Phenylurea Compounds; D011720:Pyrazoles; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; C072441:RH 3421