Invertebrate genetic screens have identified several genes with clear effects on response to ethanol and inhaled anesthetics. In Caenorhabditis elegans (C. elegans), for example, unc-79 (and unc-80) mutants are hypersensitive to the immobilizing effects of halothane and other anesthetic agents [4], [5]. In addition, unc-79 mutants are also reported to have altered responses to the immobilizing effects of ethanol [6]. In Drosophila melanogaster (Drosophila), Krishnan and Nash identified an allele of the narrow abdomen (na) gene in a forward mutagenesis screen for halothane sensitivity [7]. The na gene product has the predicted topology of a voltage-gated cationic channel [8] but efforts to characterize it electrophysiologically were unsuccessful until recently when Ren and colleagues proposed that the mouse homolog of this channel, which they named NALCN, was a tetrodotoxin-insensitive, voltage-independent cationic (leak) channel that may be critical for altering the resting membrane potential of neurons [9]. A mouse homozygous knockout allele of the NALCN gene was perinatal lethal, perhaps due to a respiratory defect [9].
