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Pyrethroid modulation of spontaneous neuronal excitability and neurotransmission in hippocampal neurons in culture

, : Pyrethroid modulation of spontaneous neuronal excitability and neurotransmission in hippocampal neurons in culture. Neurotoxicology 29(2): 213-225

Pyrethroid insecticides have potent actions on voltage-gated sodium channels (VGSC), inhibiting inactivation and increasing channel open times. These are thought to underlie, at least in part, the clinical symptoms of pyrethroid intoxication. However, disruption of neuronal activity at higher levels of organization is less well understood. In order to characterize pyrethroid effects on neurotransmitter release and neuronal excitability in glutamatergic networks, we examined the effects of deltamethrin (DM) and permethrin (PM) on neuronal activity in hippocampal neuronal cultures using patch-clamp and microelectrode array (MEA) recordings. In the presence of inhibitors of GABA receptors, spontaneous excitatory post-synaptic currents (sEPSCs) and spontaneous spike rates were reduced in a concentration-dependent manner by both DM and PM. IC(50) values were 0.037 and 0.70microM for inhibition of sEPSCs and 0.60 and 21.8microM for inhibition of spontaneous spike rate by DM and PM, respectively. Both compounds altered burst activity by decreasing the number of spikes during spontaneous bursting, the number of sEPSCs within a bursting release event and the duration of sEPSC bursts while increasing both the interspike interval and the time between sEPSCs. Exposure of neurons to the VGSC-specific modulator veratridine had effects similar to both DM and PM, while inhibition of voltage-gated calcium channels had no effect on spontaneous spike rates. In the absence of GABA receptor antagonists, both DM and PM increased spontaneous spike rates. Altogether, these data demonstrate that DM and PM disrupt network activity in vitro, largely via a VGSC-dependent mechanism.


PMID: 18243323

DOI: 10.1016/j.neuro.2007.11.005

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