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• W4309771883 endingPage "105296" @default.
• W4309771883 startingPage "105296" @default.
• W4309771883 abstract "Microtransplantation of neurolemma tissue fragments from mammalian brain into the plasma membrane of Xenopus laevis oocytes is a tool to examine the endogenous structure and function of various ion channels and receptors associated with the central nervous system. Microtransplanted neurolemma can originate from a variety of sources, contain ion channels and receptors in their native configuration, and are applicable to examine diseases associated with different channelopathies. Here, we examined potential age-related differences in voltage-sensitive sodium channel (VSSC) expression and concentration-dependent responses to pyrethroids following the microtransplantation of juvenile or adult rat brain tissue (neurolemma) into X. laevis oocytes. Using automated western blotting, adult neurolemma exhibited a 2.5-fold higher level of expression of VSSCs compared with juvenile neurolemma. The predominant isoform expressed in both tissues was Nav1.2. However, adult neurolemma expressed 2.8-fold more Nav1.2 than juvenile and expressed Nav1.6 at a significantly higher level (2.2-fold). Microtransplanted neurolemma elicited ion currents across the plasma membrane of oocytes following membrane depolarization using two electrode voltage clamp electrophysiology. A portion of this current was sensitive to tetrodotoxin (TTX) and this TTX-sensitive current was abolished when external sodium ion was replaced by choline ion, functionally demonstrating the presence of native VSSC. Increasing concentrations of permethrin or deltamethrin exhibited concentration-dependent increases in inward TTX-sensitive current in the presence of niflumic acid from both adult and juvenile tissues following a pulsed depolarization of the oocyte plasma membrane. Concentration-dependent response curves illustrate that VSSCs associated with juvenile neurolemma were up to 2.5-fold 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 (0.6-0.8-fold) but were more sensitive at higher concentrations (up to 2.4-fold). Nonetheless, because the expected concentrations in human brains 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." @default.
• W4309771883 created "2022-11-29" @default.
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• W4309771883 creator A5091227139 @default.
• W4309771883 date "2023-01-01" @default.
• W4309771883 modified "2023-09-26" @default.
• W4309771883 title "Determination of potential toxicodynamic differences of pyrethroid insecticides on native voltage-sensitive sodium channels in juvenile versus adult rat brain" @default.
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• W4309771883 doi "https://doi.org/10.1016/j.pestbp.2022.105296" @default.
• W4309771883 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36549822" @default.
• W4309771883 hasPublicationYear "2023" @default.
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