Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.
Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.
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发表时间：
1993-09
影响因子：
3.6
通讯作者：
N. Harrison;J. L. Kugler;Mathew V. Jones;Eric P. Greenblatt;D. B. Pritchett
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作者：
N. Harrison;J. L. Kugler;Mathew V. Jones;Eric P. Greenblatt;D. B. Pritchett
利用重组人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醚与配体门控氯离子通道的相互作用。异氟醚增强了γ-氨基丁酸(GABA)激活的氯电流，在表达由α1或α2、β1和γ2亚基组合组成的异构体GABAA受体的细胞中，以及在表达仅由α和β亚基组合组成的受体的细胞中。由α2和γ2亚基组成的受体表达很低，但对异氟醚敏感。由β1和γ2亚基组成的受体不表达。异氟醚还通过同源α-甘氨酸受体增强甘氨酸激活的氯电流，但不增强表达同源Rho-1受体的细胞的GABA电流。这些结果表明，并不是所有的配体门控氯离子通道受体对异氟烷都敏感，因此，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。
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.