Functional characterization of rat ρ2 subunits expressed in HEK 293 cells
Functional characterization of rat ρ2 subunits expressed in HEK 293 cells
复制标题
DOI：
10.1111/j.1460-9568.2005.03880.x
复制
发表时间：
2005-02-01
影响因子：
3.4
通讯作者：
Pasternack, M
中科院分区：
文献类型：
--
作者：
Alakuijala, A;TalviOja, K;Pasternack, M
GABA(C)受体被认为是由Rho(1)、Rho(2)和Rho(3)亚基组成的同型或异型五聚体。先前在非洲爪哇卵母细胞中表达的大鼠Rho(2)亚单位的研究表明，它们不形成功能性的同源低聚GABA(C)受体，但确实与Rho(1)或Rho(3)亚单位结合形成异源低聚物。这些发现很难解释，因为人和鼠的Rho(2)亚单位确实形成了功能性的同源寡聚受体。此外，大鼠大脑的许多区域只表达Rho(2)亚单位转录本，根据目前可用的证据，这不会导致功能性GABA(C)受体的表达。我们在这里展示了同源大鼠Rho(2)受体可以在HEK 293细胞中表达。在哺乳动物细胞中表达的同源寡聚大鼠Rho(2)受体成熟缓慢，表现出微小但可检测到的GABA诱导电流，动力学缓慢。大鼠Rho(2)受体对印防己毒素的敏感度降低，对GABA(C)受体激动剂顺-氨基甲酸的敏感度显著降低。我们的结果首次证明了功能性同源大鼠Rho(2)受体的表达，并提示Rho(2)亚单位可能有助于大脑功能，包括在不表达其他Rho亚单位的区域。
GABA(C) receptors are thought to be homo- or heteropentamers composed of rho(1), rho(2) and rho(3) subunits. Previous work on rat rho(2) subunits expressed in Xenopus oocytes has suggested that they do not form functional homo-oligomeric GABA(C) receptors, but do combine with rho(1) or rho(3) subunits to form hetero-oligomers. These findings are difficult to interpret because both human and mouse rho(2) subunits do form functional homo-oligomeric receptors. Also, many regions of the rat brain express solely rho(2) subunit transcripts which, according to presently available evidence, would not result in expression of functional GABA(C) receptors. We show here that homomeric rat rho(2) receptors can be expressed in HEK 293 cells. Homo-oligomeric rat rho(2) receptors expressed in mammalian cells matured slowly and displayed small but detectable GABA-induced currents with slow kinetics. Rat rho(2) receptors also had a decreased sensitivity to picrotoxin and a marked sensitivity to the GABA(C) receptor agonist cis-aminocrotonic acid. Our results demonstrate for the first time the expression of functional homomeric rat rho(2) receptors, and suggest that rho(2) subunits may contribute to brain function, including in areas not expressing other rho subunits.