Identification of key amino acid residues and new compounds targeting the putative isoflurane binding site (IMAGE)
Caption
(A) Isoflurane response of RyR1 mutant in which the 4000th amino acid (methionine, M) was replaced with phenylalanine (F). Compared to the wild type (WT, normal RyR1 without mutation), the isoflurane response is reduced (mean ± standard deviation, n = 4).
(B) Loss of righting reflex of knock-in mice expressing RyR1 mutants with reduced isoflurane response (n = 11 to 14). The knock-in mice were partially less susceptible to anesthesia compared to WT mice (normal mice). Hetero: mice in which only one allele is mutated. Homo: mice in which both alleles are mutated.
(C) Loss of righting reflex of mice treated with a novel compound targeting the putative isoflurane binding site (n = 9). The sensitivity to isoflurane was increased. Note that saline has no physiological activity.
The mice illustration was modified from Openclipart (https://openclipart.org/).
Credit
Department of Systems Pharmacology, Graduate School of Medicine, UTokyo
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