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

摘要

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[har ³⁸]. Methods. The Drosophila melanogaster strains wildtype Canton-S, na[har ³⁸], sh ¹⁰² and sh ^mns, 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 sh ¹⁰² > 0,05), for sh ^mns 1.711 (1.650–1.773; n = 242; P versus WT Canton-S > 0,05). The logEC50-value for sh ¹⁰² was 1.594 (1.493–1.694; n = 261; P versus sh ^mns > 0.05). The logEC-value of na[har ³⁸] was 2.076 (1.619–2.532; n = 207; P versus sh ^mns < 0.05, versus sh ¹⁰² < 0.05, versus WT Canton-S < 0.05). P values for all shaker mutants were P > 0.05, while na[har ³⁸] 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.