The Shaker Potassium Channel Is No Target for Xenon Anesthesia in Short-Sleeping Drosophila melanogaster Mutants

Abstract

Background. Xenon seems to be an ideal anesthetic drug. To explore if next to the antagonism at the NMDA-receptor other molecular targets are involved, we tested the xenon requirement in short sleeping Drosophila shaker mutants and in 𝑛𝑎[ℎ𝑎𝑟38]. Methods. The Drosophila melanogaster strains wildtype Canton-S, 𝑛𝑎[ℎ𝑎𝑟38], 𝑠ℎ102 and 𝑠ℎ𝑚𝑛𝑠, were raised and sleep was measured. Based on the response of the flies at different xenon concentrations, logEC50 values were calculated. Results. The logEC50-values for WT Canton-S were 1.671 (1.601–1.742 95%-confidence intervall; 𝑛=238; P versus 𝑠ℎ102 > 0,05), for 𝑠ℎ𝑚𝑛𝑠 1.711 (1.650–1.773; 𝑛=242; P versus WT Canton-S > 0,05). The logEC50-value for 𝑠ℎ102 was 1.594 (1.493–1.694; 𝑛=261; P versus 𝑠ℎ𝑚𝑛𝑠 > 0.05). The logEC-value of 𝑛𝑎[ℎ𝑎𝑟38] was 2.076 (1.619–2.532; 𝑛=207; P versus 𝑠ℎ𝑚𝑛𝑠 0.05, while 𝑛𝑎[ℎ𝑎𝑟38] was found to be hyposensitive compared to wildtype (P < 0.05). Conclusions. The xenon requirement in Drosophila melanogaster is not influenced by a single gene mutation at the shaker locus, whereas a reduced expression of a nonselective cation channel leads to an increased xenon requirement. This supports the thesis that xenon mediates its effects not only via an antagonism at the NMDA-receptor.