Lei Saobo, Deng Pan-Yue, Porter James E, Shin Hee-Sup
Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
J Neurophysiol. 2007 Nov;98(5):2868-77. doi: 10.1152/jn.00679.2007. Epub 2007 Sep 5.
Whereas the entorhinal cortex (EC) receives noradrenergic innervations from the locus coeruleus of the pons and expresses adrenergic receptors, the function of norepinephrine (NE) in the EC is still elusive. We examined the effects of NE on GABA(A) receptor-mediated synaptic transmission in the superficial layers of the EC. Application of NE dose-dependently increased the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from the principal neurons in layer II/III through activation of alpha(1) adrenergic receptors. NE increased the frequency and not the amplitude of miniature IPSCs (mIPSCs) recorded in the presence of TTX, suggesting that NE increases presynaptic GABA release with no effects on postsynaptic GABA(A) receptors. Application of Ca(2+) channel blockers (Cd(2+) and Ni(2+)), omission of Ca(2+) in the extracellular solution, or replacement of extracellular Na(+) with N-methyl-D-glucamine (NMDG) failed to alter NE-induced increase in mIPSC frequency, suggesting that Ca(2+) influx through voltage-gated Ca(2+) or other cationic channels is not required. Application of BAPTA-AM, thapsigargin, and ryanodine did not change NE-induced increase in mIPSC frequency, suggesting that Ca(2+) release from intracellular stores is not necessary for NE-induced increase in GABA release. Whereas alpha(1) receptors are coupled to G(q/11) resulting in activation of the phospholipase C (PLC) pathway, NE-mediated facilitation of GABAergic transmission was independent of PLC, protein kinase C, and tyrosine kinase activities. Our results suggest that NE-mediated facilitation of GABAergic function contributes to its antiepileptic effects in the EC.
虽然内嗅皮质（EC）接受来自脑桥蓝斑核的去甲肾上腺素能神经支配并表达肾上腺素能受体，但去甲肾上腺素（NE）在EC中的功能仍不清楚。我们研究了NE对EC浅层中GABA(A)受体介导的突触传递的影响。应用NE剂量依赖性地增加了从II/III层主要神经元记录的自发性抑制性突触后电流（IPSCs）的频率和幅度，这是通过激活α(1)肾上腺素能受体实现的。NE增加了在存在TTX时记录的微小IPSCs（mIPSCs）的频率而非幅度，表明NE增加了突触前GABA的释放，而对突触后GABA(A)受体没有影响。应用Ca(2+)通道阻滞剂（Cd(2+)和Ni(2+)）、细胞外溶液中省略Ca(2+)或用N-甲基-D-葡萄糖胺（NMDG）替代细胞外Na(+)均未能改变NE诱导的mIPSC频率增加，表明不需要通过电压门控Ca(2+)或其他阳离子通道的Ca(2+)内流。应用BAPTA-AM、毒胡萝卜素和ryanodine并没有改变NE诱导的mIPSC频率增加，表明从细胞内储存释放Ca(2+)对于NE诱导的GABA释放增加不是必需的。虽然α(1)受体与G(q/11)偶联导致磷脂酶C（PLC）途径的激活，但NE介导的GABA能传递促进作用独立于PLC、蛋白激酶C和酪氨酸激酶活性。我们的结果表明，NE介导的GABA能功能促进作用有助于其在EC中的抗癫痫作用。
