A single nucleotide polymorphism in GABAA receptor isoforms is potentially responsible for isoflurane sensitivity in mice.

GABAA receptors are chloride channels in the brain that are activated by binding with g-aminobutyric acid (GABA). The cDNA sequences of GABAA receptor subunits from two strains of mice with different sensitivities to isoflurane were compared to identify nucleotide mutations. Included 80 mice from two strains with different sensitivities to isoflurane on C57BL/6 background. Forty mice were from an isoflurane-sensitive strain (S group) and 40 mice were from a resistant strain (R group). RNA was extracted from brains of the mice, and cDNA were reverse transcribed using AMV reverse transcriptase. The amplified products were processed, sequenced, and analyzed for differences between the two strains. Chi-square analysis was performed to compare differences in nucleotide mutation frequencies between the two strains. No differences were identified in the α1-6, β2, β3, or γ1-3 nucleotide sequences and no single nucleotide polymorphisms were found in the comparison with the GenBank sequence for the GABAA receptor subunit. A single nucleotide polymorphism (SNP) at the nucleotide position 462 (C/G) in the β1 sequence was found. This SNP was observed in 5 mice from the sensitive strain and in 36 mice from the resistant strain. The Fischer exact test (P < 0.01) was used to compare two strains of mice for SNP in the cDNA sequence of the β1 subunit. Additional studies are required to understand whether the GABAA receptor is a specific target of inhaled anesthetic action or whether the identified SNP affects the action of the volatile anesthetic.