An ion channel that influences anesthesia sensitivity: Designing a genetic test for assessing a candidate anesthetic target

Mutations in a gene that encodes an unusual ion channel significantly change the sensitivity of Drosophila to volatile anesthetics (VAs). As for any gene implicated by mutation, we would like to know whether the corresponding gene product is a mediator or modulator of anesthesia. After reviewing what is known about the ion channel gene and the mutant phenotype, we present a theoretical framework for testing the involvement of this (or any) gene product as a direct target of VAs. In essence, we propose that manipulating the copy number of a bona fide target gene should result in alterations of anesthetic sensitivity. A positive feature of this strategy is that it tends to limit compensatory effects. On the other hand, we discuss how false negatives and false positives could obscure the outcome. Nevertheless, the simplicity and clarity of the approach recommends it as a general tool; testing of the ion channel gene is under way.