Effects of n-hexane and its metabolites on cloned voltage-operated neuronal potassium channels.
In order to study the mechanisms of acute n-hexane intoxication, the effects of n-hexane and its metabolites 2-hexanol, methyl-n-butyl ketone, 2,5-hexanediol and 2,5-hexanedione on the cloned voltage-operated potassium channels Kv1.1, Kv1.4, Kv2.1 and Kv3.4 were investigated with electrophysiological techniques in the expression system of Xenopus oocytes. n-Hexane had no effect at any channel, whereas some of its metabolites led to reductions of the potassium currents. The greatest effects obtained were caused by 2-hexanol at the Kv2.1 channel, resulting in reductions of 13% at 0 mV with a concentration of 500 mg/l and IC50 of ca. 3500 mg/l. The reduction appeared to be caused by a shift of the current-voltage relation to the right. Methyl-n-butyl ketone showed smaller effects, whereas 2,5-hexanedione and 2,5-hexandiol were nearly ineffective. Concerning the different potassium channels, the sensitivity to the metabolites differed. The metabolites showed greatest sensitivity towards the Kv2.1 channel and lowest sensitivity towards the Kv3.4 channel. Since the n-hexane metabolite concentrations in the brain during acute n-hexane intoxication are unknown, the relevance of the data is still unclear. The size of the effects and the currently available data on tissue concentration, however, make it more likely that the action of n-hexane and its metabolites on voltage-operated potassium channels is not a major mechanism for acute neurotoxicity.
Madeja
M
M
Institut für Physiologie, Münster, Germany.
Binding
N
N
Musshoff
U
U
Witting
U
U
Speckmann
E J
EJ
D000818:Animals; D006586:Hexanes / Q000378:metabolism / Q000633:toxicity*; D000441:Hexanols / Q000633:toxicity*; D006588:Hexanones / Q000633:toxicity*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics; D014162:Transfection; D014982:Xenopus laevis
D006586:Hexanes; D000441:Hexanols; D006588:Hexanones; D015221:Potassium Channels; C026385:n-hexane; C037076:2-hexanol; C011269:2,5-hexanedione