Underlying mechanism of actions of tefluthrin, a pyrethroid insecticide, on voltage-gated ion currents and on action currents in pituitary tumor (GH3) cells and GnRH-secreting (GT1-7) neurons

Tefluthrin is a synthetic pyrethroid and involved in acute neurotoxic effects. How this compound affects ion currents in endocrine or neuroendocrine cells remains unclear. Its effects on membrane ion currents in pituitary tumor (GH(3)) cells and in hypothalamic (GT1-7) neurons were investigated. Application of Tef (10 mu M) increased the amplitude of voltage-gated Na+ current (I-Na), along with a slowing in current inactivation and deactivation in GH3 cells. The current-voltage relationship of I-Na was shifted to more negative potentials in the presence of this compound. Tef increased INa with an EC50 value of 3.2 +/- 0.8 mu M It also increased the amplitude of persistent IN,. Tef reduced the amplitude of L-type Ca2+ current. This agent slightly inhibited K+ outward current; however, it had no effect on the activity of large-conductance Ca2+-activated K+ channels. Under cell-attached voltage-clamp recordings, Tef (10 mu M) increased amplitude and frequency of spontaneous action currents, along with appearance of oscillatory inward currents. Tef-induced inward currents were suppressed after further application of tetrodotoxin, riluzole or ranolazine. In GT1-7 cells, Tef also increased the amplitude and frequency of action currents. Taken together, the effects of Tef and its structural related pyrethroids on ion currents can contribute to the underlying mechanisms through which they affect endocrine or neuroendocrine function in vivo. (C) 2009 Elsevier Ireland Ltd. All rights reserved.