Extrasynaptic αβ subunit GABA A receptors on rat hippocampal pyramidal neurons

作者：Martin Nordvig Mortensen, Trevor G. Smart · 发表于：The Journal of Physiology · 年份：2006 · DOI：10.1113/jphysiol.2006.117952 · 被引用次数：167 · 研究领域：Neuroscience and Neuropharmacology Research、Neural dynamics and brain function、Neuroinflammation and Neurodegeneration Mechanisms

Extrasynaptic GABA(A) receptors that are tonically activated by ambient GABA are important for controlling neuronal excitability. In hippocampal pyramidal neurons, the subunit composition of these extrasynaptic receptors may include alpha5betagamma and/or alpha4betadelta subunits. Our present studies reveal that a component of the tonic current in the hippocampus is highly sensitive to inhibition by Zn(2+). This component is probably not mediated by either alpha5betagamma or alpha4betadelta receptors, but might be explained by the presence of alphabeta isoforms. Using patch-clamp recording from pyramidal neurons, a small tonic current measured in the absence of exogenous GABA exhibited both high and low sensitivity to Zn(2+) inhibition (IC(50) values, 1.89 and 223 microm, respectively). Using low nanomolar and micromolar GABA concentrations to replicate tonic currents, we identified two components that are mediated by benzodiazepine-sensitive and -insensitive receptors. The latter indicated that extrasynaptic GABA(A) receptors exist that are devoid of gamma2 subunits. To distinguish whether the benzodiazepine-insensitive receptors were alphabeta or alphabetadelta isoforms, we used single-channel recording. Expressing recombinant alpha1beta3gamma2, alpha5beta3gamma2, alpha4beta3delta and alpha1beta3 receptors in human embryonic kidney (HEK) or mouse fibroblast (Ltk) cells, revealed similar openings with high main conductances (approximately 25-28 pS) for gamma2 or delta subuni...