Inhibition of a neuronal voltage-dependent chloride channel by the type II pyrethroid, deltamethrin.
Following the previous finding that the Type II pyrethroid, deltamethrin, increased membrane resistance in peripheral nerve and muscle in a chloride-dependent manner, the action of deltamethrin on neuronal voltage-dependent chloride channels was assessed using inside-out patches from NIE-115 neuroblastoma cells. These were bathed in symmetrical solutions, containing 149 mM chloride and the membrane potential stepped from 0 mV to voltages ranging from +/- 10 to 80 mV for 2 or 5 sec. Active patches contained large conductance channels (343 +/- 11 pS, n = 8), which inactivated relatively slowly during the voltage step and could be resolved into a number of substates. The channels were confirmed as being chloride specific on the basis of substitution experiments with isethionate and pharmacological blockade by 9-anthracene carboxylic acid (9-ACA). Within 20 min of adding deltamethrin (2 microM) to the bath solution, open channel probability (Po) fell from 0.50 +/- 0.06 to 0.24 +/- 0.04 (n = 11) a highly significant result. Glycerinformal solvent alone (0.1% v/v) caused a non-significant rise to 0.65 +/- 0.09 (n = 4). The decreased open channel probability after deltamethrin was due to an increased incidence of both the closed channel state and low conductance substates. In addition, deltamethrin frequently caused flickering between substrates similar to that seen after 9-ACA. Deltamethrin did not change single channel conductance, current-voltage relationship or time-dependent channel inactivation, but decreased open channel probability over the complete range of membrane voltage tested.(ABSTRACT TRUNCATED AT 250 WORDS)
MRC Toxicology Unit, MRC Laboratories, Carshalton, Surrey, U.K.
P J
PJ
Forshaw
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Lister
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Ray
D000818:Animals; D018118:Chloride Channels; D004594:Electrophysiology; D007306:Insecticides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles; D011722:Pyrethrins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D018118:Chloride Channels; D007306:Insecticides; D008565:Membrane Proteins; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin