Blockage of one class of potassium channel alters the effectiveness of halothane in a brain circuit of Drosophila.
At concentrations comparable to those used in the clinic, halothane has profound effects on a neuronal pathway devoted to the escape reflex of the fruit fly, Drosophila melanogaster. We studied the influence of the potassium channel that is encoded by the Shaker gene on the halothane sensitivity of this circuit. Shaker channels were specifically inactivated either by genetic means, using strains with two different severe Shaker mutations, or by pharmacologic means, using ingestion of millimolar concentrations of 4-aminopyridine. In all cases, halothane potency decreased substantially. To ensure that the genetic alteration was specific, both mutations were studied as stocks that had been repeatedly backcrossed to a control strain. The specificity of the pharmacologic inhibition was demonstrated by the fact that 4-aminopyridine had no effect on halothane potency in a Shaker mutant. Quantitative differences in the effects of channel inhibition between males and females suggested a sexual dimorphism in the functional brain anatomy of the reflex circuit.
Walcourt
A
A
Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892-4034, USA.
Scott
R L
RL
Nash
H A
HA
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004330:Drosophila / Q000187:drug effects*; D029721:Drosophila Proteins; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D009154:Mutation; D015221:Potassium Channels / Q000502:physiology*; D012727:Sex Characteristics; D051637:Shaker Superfamily of Potassium Channels
D018685:Anesthetics, Inhalation; D029721:Drosophila Proteins; D015221:Potassium Channels; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels; D006221:Halothane