Abstract
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 μM) increased the amplitude of voltage-gated Na + current ( I Na), along with a slowing in current inactivation and deactivation in GH 3 cells. The current–voltage relationship of I Na was shifted to more negative potentials in the presence of this compound. Tef increased I Na with an EC 50 value of 3.2 ± 0.8 μM. It also increased the amplitude of persistent I Na. Tef reduced the amplitude of L-type Ca 2+ current. This agent slightly inhibited K + outward current; however, it had no effect on the activity of large-conductance Ca 2+-activated K + channels. Under cell-attached voltage-clamp recordings, Tef (10 μM) 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.
Published Version
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