Single channel study of deltamethrin interactions with wild-type and mutated rat Na(V)1.2 sodium channels expressed in Xenopus oocytes.
Single channel analysis was used to compare the electrophysiological properties of wild-type (WT) and I874M mutant (M874) rat Na(V)1.2 channels expressed in Xenopus oocytes and their modulation by the pyrethroid deltamethrin. In the absence of pyrethroid, histograms of channel open times were best-fit by single exponentials. The open time constants at -40 mV for WT (0.53+/-0.05 ms) and M874 (0.65+/-0.08 ms) channels were significantly different and both decreased with depolarisation. At > or =100 nM deltamethrin, WT open time histograms at -40 mV were best-fit by two exponentials (time constants, 0.49+/-0.03 ms (tau(o,fast,WT)) and 5.2+/-0.5 ms (tau(o,slow,WT)). The population of long-duration openings and tau(o,slow,WT) increased when the concentration of deltamethrin was raised, but tau(o,fast,WT) was unaffected. Qualitatively similar results were obtained for the M874 channel, but with > or =10 nM deltamethrin. Deltamethrin also caused a negative shift in the relationships between channel opening probability (P(op)) and membrane potential and first latency and membrane potential, suggesting that the pyrethroid binds to the closed channel. Selectivity for Na was increased by the pyrethroid (10 microM, WT; 1 microM, mutant).
Peng
Fang
F
School of Biology, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom.
Mellor
Ian R
IR
Williamson
Martin S
MS
Davies
T G Emyr
TG
Field
Linda M
LM
Usherwood
Peter N R
PN
D000818:Animals; D055724:Electrophysiological Phenomena; D005260:Female; D007306:Insecticides / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009570:Nitriles / Q000494:pharmacology*; D009865:Oocytes; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D015222:Sodium Channels / Q000235:genetics* / Q000502:physiology*; D014162:Transfection; D014982:Xenopus laevis
D007306:Insecticides; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009570:Nitriles; D011722:Pyrethrins; C568253:Scn2A protein, rat; D015222:Sodium Channels; C017180:decamethrin