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GENERAL ARTICLES

Blockage of One Class of Potassium Channel Alters the Effectiveness of Halothane in a Brain Circuit of Drosophila

Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland

Address correspondence and reprint requests to Howard A. Nash, MD, PhD, Bldg. 36, Rm. 1B08, LMB, NIMH, Bethesda MD 20892-4034.

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.

Implications: Shaker channels are important elements during halothane inhibition of a specific reflex in Drosophila. Neurons that express these channels, which are irregularly distributed in the brain of flies, provide promising leads to identifying anesthetic-sensitive components.

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