Poisbeau P, Cheney M C, Browning M D, Mody I
Laboratoire de Neurophysiologie Cellulaire et Intégrée, Centre National de la Recherche Scientifique UMR 7519, Université Louis Pasteur, 67084 Strasbourg, France.
J Neurosci. 1999 Jan 15;19(2):674-83. doi: 10.1523/JNEUROSCI.19-02-00674.1999.
Several protein kinases are known to phosphorylate Ser/Thr residues of certain GABAA receptor subunits. Yet, the effect of phosphorylation on GABAA receptor function in neurons remains controversial, and the functional consequences of phosphorylating synaptic GABAA receptors of adult CNS neurons are poorly understood. We used whole-cell patch-clamp recordings of GABAA receptor-mediated miniature IPSCs (mIPSCs) in CA1 pyramidal neurons and dentate gyrus granule cells (GCs) of adult rat hippocampal slices to determine the effects of cAMP-dependent protein kinase (PKA) and Ca2+/phospholipid-dependent protein kinase (PKC) activation on the function of synaptic GABAA receptors. The mIPSCs recorded in CA1 pyramidal cells and in GCs were differentially affected by PKA and PKC. In pyramidal cells, PKA reduced mIPSC amplitudes and enhanced the fraction of events decaying with a double exponential, whereas PKC was without effect. In contrast, in GCs PKA was ineffective, but PKC increased the peak amplitude of mIPSCs and also favored double exponential decays. Intracellular perfusion of the phosphatase inhibitor microcystin revealed that synaptic GABAA receptors of pyramidal cells, but not those of GCs, are continually phosphorylated by PKA and conversely, dephosphorylated, most likely by phosphatase 1 or 2A. This differential, brain region-specific phosphorylation of GABAA receptors may produce a wide dynamic range of inhibitory synaptic strength in these two regions of the hippocampal formation.
已知几种蛋白激酶可使某些GABAA受体亚基的丝氨酸/苏氨酸残基磷酸化。然而，磷酸化对神经元中GABAA受体功能的影响仍存在争议，而且对成体中枢神经系统神经元突触GABAA受体磷酸化的功能后果了解甚少。我们采用全细胞膜片钳记录成年大鼠海马脑片CA1锥体神经元和齿状回颗粒细胞（GCs）中GABAA受体介导的微小抑制性突触后电流（mIPSCs），以确定环磷酸腺苷依赖性蛋白激酶（PKA）和Ca2+/磷脂依赖性蛋白激酶（PKC）激活对突触GABAA受体功能的影响。在CA1锥体细胞和GCs中记录到的mIPSCs受PKA和PKC的影响不同。在锥体细胞中，PKA降低了mIPSC的幅度，并增加了以双指数衰减的事件比例，而PKC则无作用。相反，在GCs中PKA无效，但PKC增加了mIPSCs的峰值幅度，也有利于双指数衰减。细胞内灌注磷酸酶抑制剂微囊藻毒素显示，锥体细胞的突触GABAA受体持续被PKA磷酸化，而GCs的突触GABAA受体则相反，很可能被磷酸酶1或2A去磷酸化。GABAA受体这种不同的、脑区特异性的磷酸化可能在海马结构的这两个区域产生广泛的抑制性突触强度动态范围。
