Rat brain neurolemma microtransplanted  into the plasma membrane of <i>Xenopus laevis</i> oocytes is an <i>ex vivo</i> method used to study channels and receptors in their native state using standard electrophysiological approaches. We previously reported that oocytes injected with rat brain neurolemma elicited tetrodotoxin-sensitive, inward ion currents upon membrane depolarization, which were increased by treatment with the pyrethroid insecticides, permethrin and deltamethrin. The data obtained, however, were highly variable. A collection of changes to the assay procedure, data acceptance criteria, and analysis method yielded substantially improved precision and hence, assay performance. Using these improvements, we examined potential age-related differences in voltage-sensitive sodium channel (VSSC) expression and concentration-dependent responses to pyrethroids. VSSCs associated with juvenile neurolemma were up to 2.5X more sensitive to deltamethrin than VSSCs in adult neurolemma. In contrast, VSSCs from juvenile neurolemma were less sensitive to permethrin than adult VSSCs at lower concentrations (0.6-0.8X) but were more sensitive at higher concentrations (up to 2.4X). Nonetheless, because the expected brain concentrations in humans following realistic exposure levels are approximately 21- (deltamethrin) to 333- (permethrin) times below the threshold concentration for response in rat neurolemma-injected oocytes, age-related differences, if any, are not likely to be toxicologically relevant.

Age-related difference in the action of pyrethroids on native voltage-sensitive sodium channels from juvenile and adult rat brains

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