Temperature dependence of pyrethroid modification of single sodium channels in rat hippocampal neurons

Pyrethroid modulation of sodium channels is unique in the sense that it is highly dependent on temperature, the potency being augmented by lowering th e temperature. To elucidate the mechanisms underlying the negative temperat ure dependence of pyrethroid action, single sodium channel currents were re corded from cultured rat hippocampal neurons using the inside-out configura tion of patch-clamp technique, and the effects of the pyrethroid tetramethr in were compared at 22 and 12 degrees C. Tetramethrin-modified sodium chann els opened with short closures and/or transitions to subconductance levels at 22 and 12 degrees C. The time constants of the burst length histograms f or tetramethrin-modified channels upon depolarization to -60 mV were 7.69 a nd 14.46 msec at 22 and 12 degrees C, respectively (Q(10) = 0.53). Tetramet hrin at 10 mu M modified 17 and 23% of channels at 22 and 12 degrees C, res pectively, indicating that the sensitivity of the sodium channel of rat hip pocampal neurons to tetramethrin was almost the same as that of tetrodotoxi n-sensitive sodium channels of rat dorsal root ganglion neurons and rat cer ebellar Purkinje neurons. The time constants for burst length in tetramethr in-modified sodium channels upon repolarization to -100 mV from -30 mV were 8.26 and 68.80 msec at 22 and 12 degrees C (Q(10) = 0.12), respectively. T he prolongation of tetramethrin-modified whole-cell sodium tail currents up on repolarization at lower temperature was ascribed to a prolongation of op ening of each channel. Simple state models were introduced to interpret beh aviors of tetramethrin-modified sodium channels. The Q(10) values for trans ition rate constants upon repolarization were extremely large, indicating t hat temperature had a profound effect on tetramethrin-modified sodium chann els.