Harrison N L, Kugler J L, Jones M V, Greenblatt E P, Pritchett D B
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
Mol Pharmacol. 1993 Sep;44(3):628-32.
The interactions of the inhalation anesthetic agent isoflurane with ligand-gated chloride channels were studied using transient expression of recombinant human receptors in a mammalian cell line. Isoflurane enhanced gamma-aminobutyric acid (GABA)-activated chloride currents in cells that expressed heteromeric GABAA receptors consisting of combinations of alpha 1 or alpha 2, beta 1, and gamma 2 subunits and in cells that expressed receptors consisting of combinations of only alpha and beta subunits. Receptors consisting of alpha 2 and gamma 2 subunits were poorly expressed but were sensitive to isoflurane. Receptors consisting of beta 1 and gamma 2 subunits were not expressed. Isoflurane also enhanced glycine-activated chloride currents through homomeric alpha glycine receptors but did not enhance GABA currents in cells expressing homomeric rho 1 receptors. These results show that not all ligand-gated chloride channel receptors are sensitive to isoflurane and, therefore, that the anesthetic interacts with specific structural determinants of these ion channel proteins.
利用重组人类受体在哺乳动物细胞系中的瞬时表达，研究了吸入麻醉剂异氟烷与配体门控氯离子通道的相互作用。异氟烷增强了表达由α1或α2、β1和γ2亚基组合而成的异聚GABAA受体的细胞以及表达仅由α和β亚基组合而成的受体的细胞中γ-氨基丁酸（GABA）激活的氯离子电流。由α2和γ2亚基组成的受体表达水平较低，但对异氟烷敏感。由β1和γ2亚基组成的受体未表达。异氟烷还通过同源α甘氨酸受体增强了甘氨酸激活的氯离子电流，但在表达同源ρ1受体的细胞中未增强GABA电流。这些结果表明，并非所有配体门控氯离子通道受体都对异氟烷敏感，因此，该麻醉剂与这些离子通道蛋白的特定结构决定因素相互作用。
