title: Differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant single sodium channels.
abstract: The differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) single sodium channel currents in rat dorsal root ganglion (DRG) neurons were investigated using the outside-out configuration of patch-clamp technique. Channel conductances were 10.7 and 6.3 pS for TTX-S and TTX-R sodium channels, respectively, at a room temperature of 24-26 degrees C. The single-channel current of TTX-S sodium channels at the test potential of -30 mV was -1.27 +/- 0.25 pA, and was not changed after exposure to 10 microM tetramethrin (-1.28 +/- 0.23 pA). The open time histogram of TTX-S single-channel currents could be fitted by a single exponential function with a time constant of 1.27 ms. After exposure to 10 microM tetramethrin, the open time histogram could be fitted by the sum of two exponential functions with time constants of 1.36 ms (tau fast) and 5.73 ms (tau slow). The percentage of contribution of each component to the population was 62% for the fast component representing the normal channels and 38% for the slow component representing the tetramethrin modified channels. The amplitude of TTX-R single-channel currents was slightly changed from -0.72 +/- 0.14 to -0.83 +/- 0.07 pA by 10 microM tetramethrin. The open time histogram of TTX-R single-channel currents could be fitted by a single exponential function with a time constant of 1.92 ms. In the presence of 10 microM tetramethrin, the open time histogram could be fitted by the sum of two exponential functions with time constants of 2.07 ms (tau fast) and 9.75 ms (tau slow). The percentage of contribution of each component was 15% for the fast, unmodified component and 85% for the slow, modified component. Differential effects of tetramethrin on the open time distribution of single sodium channel currents explains the differential sensitivity of TTX-S and TTX-R sodium channels.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Song
authors.forename: T
authors.initials: T
authors.lastname: Narahashi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D007306:Insecticides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010477:Perfusion; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D007306:Insecticides; D011722:Pyrethrins; D015222:Sodium Channels; D013779:Tetrodotoxin; C009424:tetramethrin