White Anne-Marie, Platt Bettina
Department of Biomedical Sciences, Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen, AB25 2ZD, Scotland, UK.
Neurosci Lett. 2002 Dec 13;334(2):79-82. doi: 10.1016/s0304-3940(02)01059-5.
Ionotropic gamma-aminobutyric acid (GABA) receptors are known to mediate excitation in neonatal neurones as a crucial developmental factor. In the present study we employed calcium imaging techniques with the calcium indicator Fura-2-AM to study the pharmacology of GABA-induced calcium responses in cultures prepared from neonatal rat superficial superior colliculus (SC), after immunocytochemical labelling confirmed the presence of GABA(C) rho(1) subunits in 35% of neurones. Rises in neuronal intracellular calcium were obtained in response to GABA and also to the subtype-specific GABA(A) agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol. However, the GABA(C) agonist cis-4-aminocrotonic acid induced calcium response only at unspecifically high concentrations (500 microM). Co-application of GABA antagonists revealed that both GABA(A&C) agonists' actions could be blocked by the GABA(A) antagonist bicuculline but not the GABA(C) antagonists 1,2,5,6-tetrahydro-(pyridin-4-yl) methylphosphinic acid. This suggests that activation of GABA(A) but not GABA(C) receptors contributes to excitatory GABA responses and related calcium signals in neonatal SC neurones.
离子型γ-氨基丁酸(GABA)受体作为一种关键的发育因子,已知其在新生神经元中介导兴奋作用。在本研究中,我们采用钙成像技术,使用钙指示剂Fura-2-AM,研究新生大鼠上丘浅层(SC)培养物中GABA诱导的钙反应的药理学特性,免疫细胞化学标记证实35%的神经元中存在GABA(C) ρ(1)亚基。神经元细胞内钙升高是对GABA以及亚型特异性GABA(A)激动剂4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇的反应。然而,GABA(C)激动剂顺式-4-氨基巴豆酸仅在非特异性高浓度(500微摩尔)时诱导钙反应。GABA拮抗剂的共同应用表明,GABA(A&C)激动剂的作用均可被GABA(A)拮抗剂荷包牡丹碱阻断,但不能被GABA(C)拮抗剂1,2,5,6-四氢-(吡啶-4-基)甲基次膦酸阻断。这表明GABA(A)受体而非GABA(C)受体的激活有助于新生SC神经元中兴奋性GABA反应及相关钙信号。