Fipronil modulation of GABAA receptor single-channel currents

Fipronil is the first phenylpyrazole insecticide introduced for pest control. Although fipronil is known to inhibit GABA receptors, the detailed mechanism of action remains to be seen. In order to elucidate the mechanism of fipronil interaction with the mammalian GABA(A) system, single-channel patch clamp experiments were performed using rat dorsal root ganglion neurons. The amplitude of main conductance state (27 pS) current was not significantly altered by co-application of 10 muM fipronil and 10 muM GABA. The histograms of open time distribution were fitted to a sum of three exponential functions. After application of 10 muM fipronil, the proportion of the fastest component increased slightly and that of the slowest component decreased slightly. Thus, the mean open time was decreased from 11.4 ms to 7.8 ms by fipronil. The histograms of closed time distribution were fitted to a sum of four exponential functions. Fipronil 10 muM prolonged the slowest time constant resulting in a prolongation of the mean closed time from 29.7 ms to 52.8 ms. Thus, the frequency of channel openings was reduced. Thus, the fipronil suppression of GABA-induced whole-cell currents is caused in part by decreases in the channel open time and the frequency of channel openings. (C) 2004 Society of Chemical Industry