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ADULT AND JUVENILE RAT SODIUM CHANNEL (NAV1.2 AND NAV1.3) SENSITIVITY TO THE PYRETHROID INSECTICIDE DELTAMETHRIN.
Citation:
MEACHAM, C. A., P. BRODFUEHRER, A. BALE, J. WATKINS, K. M. CROFTON, AND TIM J. SHAFER. ADULT AND JUVENILE RAT SODIUM CHANNEL (NAV1.2 AND NAV1.3) SENSITIVITY TO THE PYRETHROID INSECTICIDE DELTAMETHRIN. Presented at International Neurotoxicology Conference, Research Triangle Park, NC, September 11 - 14, 2005.
Description:
Adult rats are less sensitive than juveniles to the acute neurotoxicity of the Type II pyrethroid insecticide deltamethrin (DLT). Voltage-sensitive sodium channels (VSSCs) are the primary target of DLT and are differentially expressed during development, with expression of Nav1.2 predominating in the adult CNS, and Nav1.3 predominating in the embryo and juvenile animal. To investigate the hypothesis that pharmacodynamic differences contribute to the differential sensitivity of young animals to DLT, effects of DLT on Nav1.2 and Nav1.3 were compared following expression of these channels in Xenopus laevis oocytes. Two electrode voltage clamp recordings demonstrated expression of VSSCs in oocytes injected with either Nav1.2 or Nav1.3 mRNA in the absence or presence of �1 subunit mRNA. Tetrodotoxin (1 �M) demonstrated channel specificity by blocking peak and tail current through both channels. DLT increased tail currents in both Nav1.2 and Nav1.3-injected oocytes in a concentration-dependent manner, with 0.1 and 1.0 �M DLT significantly increasing tail current amplitude after 2 min of exposure. DLT (0.1 �M and 1 �M) increased tail current by 51.21 � 5.82 and 134.15 � 14.09 (n=18) percent over control respectively in oocytes expressing Nav1.2/�1; by 76.38 � 11.81 (n=19) and 106.36 � 8.99 (n=15) in Nav1.3/�1; and by 42.07 � 13.87 (n=6) and 71.79 � 11.47 (n=6) in Nav1.3/No�1 (without �1). These results demonstrate that both Nav1.2 and Nav1.3 are sensitive to DLT; and VSSCs may be less sensitive to pyrethroids without co-expression with � subunits. These results may partially account for the differential sensitivity of juvenile and adult animals to the acute neurotoxicity of DLT. (This work was supported by the U.S. EPA and does not necessarily reflect EPA policy).