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ACTIONS OF PYRETHROID INSECTICIDES ON THE SPONTANEOUS RELEASE OF GLUTAMATE FROM CULTURED HIPPOCAMPAL NEURONS.
Citation:
Meyer, D. A. AND T J. Shafer. ACTIONS OF PYRETHROID INSECTICIDES ON THE SPONTANEOUS RELEASE OF GLUTAMATE FROM CULTURED HIPPOCAMPAL NEURONS. Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Description:
Pyrethroid insecticides increase the excitability of the central and peripheral nervous systems. Modulation of voltage-gated sodium channels is likely to play a primary role in this effect, but recent studies have suggested that pyrethroid effects on other ion channels may contribute to increased excitability of neurons. Pyrethroid modulation of neuronal excitability, regardless of the target site, ultimately manifest as changes in neurotransmitter release. However, very few studies have utilized neurophysiological approaches to examine directly pyrethroid effects on neurotransmitter release in either the central or peripheral nervous systems of mammals. The present studies examined the effects of two pyrethroids on glutamate release using whole-cell patch clamp recordings from pyramidal neurons in mixed hippocampal cultures. Under control conditions, spontaneous action potential-induced glutamate release was observed as regular bursts of excitatory post-synaptic currents with average interevent intervals of 143 msec (range = 50 - 300 msec, n = 33 neurons). In the presence of both the Type I pyrethroid permethrin and the Type II pyrethroid deltamethrin, the average interevent interval within each burst increased in a concentration dependent manner between 10 nM and 10 M with approximate EC50s of 710 and 37 nM for permethrin (n = 3-5 neuons/concentration) and deltamethrin (n = 3-6 neurons/concentration), respectively. At 10 M, interevent intervals were 90% by deltamethrin (n = 3) and permethrin, (n = 3), respectively. This increase in time between events within individual bursts of glutamate release indicates that exposure to these pyrethroids alters the basal pattern of glutamate release from hippocampal neurons in culture. The role of various ion channels in this effect remains to be investigated. (This abstract does not necessarily reflect EPA policy).