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CONCENTRATION DEPENDENT ACCUMULATION OF [3H]-DELTAMETHRIN IN XENOPUS LAEVIS OOCYTES.
Citation:
WATKINS, J., C. A. MEACHAM, A. BALE, K. M. CROFTON, AND TIM J. SHAFER. CONCENTRATION DEPENDENT ACCUMULATION OF [3H]-DELTAMETHRIN IN XENOPUS LAEVIS OOCYTES. Presented at International Neurotoxicology Conference, Research Triangle Park, NC, September 11 - 14, 2005.
Description:
Pyrethroid insecticides such as deltamethrin have been demonstrated to target and disrupt voltage-sensitive sodium channels (VSSCs). VSSCs were expressed in Xenopus laevis oocytes and used to study the effects of deltamethrin on VSSCs. This study evaluated the amount of deltamethrin (DLT) absorption by VSSC-expressing oocytes. Previous research concerning the uptake of DLT in non-injected oocytes was performed by Harrill et al (2005). Nav 1.2 is the primary VSSC in the adult rat brain and was selected to model mammalian VSSCs in this experiment. Since deltamethrin disrupts sodium channels, it was hypothesized that oocytes expressing the Nav 1.2/�1 would have a higher uptake of [3H]-deltamethrin (DLT) than non-injected oocytes. Oocyte expression of Nav 1.2/�1 channels was assessed by two-electrode voltage-clamp. The expression rate was 98% in all experiments (n=5); deltamethrin increased tail currents for all the tested oocytes. Tetrodotoxin (TTX) was used to test for specificity of the channel, and blocked both peak and tail currents. Accumulation of DLT (0.1 and 1.0 �M) after a 1 hour exposure, in both injected and non-injected oocytes, was determined using liquid scintillation counting. There was no significant difference in DLT uptake between VSSC-injected oocytes and non-injected controls, although the transfected oocytes consistently had less accumulation. In 0.1 �M incubation solution, non-injected oocytes accumulated 0.162 � 0.076 �g [3H]-DLT, water injected oocytes accumulated 0.110 � 0.062 �g, and transfected oocytes accumulated 0.088 � 0.044 �g. In 1.0 �M incubation solution, non-injected oocytes accumulated 1.04 � 0.409 �g, water injected oocytes accumulated 0.914 � 0.447 �g, and transfected oocytes accumulated 0.804 � 0.287 �g. The results suggest that deltamethrin disrupts VSSCs and demonstrate that the presence of the channel did not cause greater accumulation. In fact, less accumulation may take place. This abstract does not reflect EPA policy.