Mammalian ryanodine receptors are known targets of the volatile general anesthetic halothane; these receptors mediate release of calcium from intracellular storage in multiple different cellular processes. There are 3 ryanodine receptors in human, RYR1, RYR2, and RYR3; there is a single orthologous gene in Drosophila, Dmel\RyR. Multiple genetic reagents have been generated for Dmel\RyR, including loss-of-function mutations, regulated expression and RNAi targeting constructs, and alleles caused by insertional mutagenesis.

None of the human genes, RYR1, RYR2 or RYR3, has been introduced into flies.

Using animals carrying mutations of RyR, response to halothane and other tested anesthetics was measured with a reactive climbing assay; wild-type animals exhibit a halothane-dependent decrease in locomotor activity. RyR loss-of-function mutations result in increased resistance to halothane; a weaker effect on the sensitivity to sevoflurane, enflurane, and isoflurane is observed. Using tissue-specific knockdown of RyR effected by RNAi, it was determined that resistance is mediated by expression of RyR in the nervous system, but not in muscle. A number of RyR missense alleles were found to increase sensitivity to halothane in heterozygous animals; these were found to map to highly conserved amino acids. Assays at the level of response of individual neurons confirm that halothane-induced Ca(2+) flux that is altered in RyR mutants.

See also the FlyBase chemical report for halothane (FBch0000344).

[updated Mar. 2024 by FlyBase; FBrf0222196]