Du C, Role L W
Department of Anatomy and Cell Biology in the Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Neurophysiol. 2001 Jun;85(6):2498-508. doi: 10.1152/jn.2001.85.6.2498.
The diversity of neuronal nicotinic acetylcholine receptors (nAChRs) is likely an important factor in the modulation of synaptic transmission by acetylcholine and nicotine. We have tested whether postsynaptic nAChRs are modulated in a subtype-specific manner by prostaglandin E(2) (PGE(2)), a regulator of neuronal excitability in both the central and peripheral nervous systems, and examined the effects of PGE(2) on nicotinic transmission. Somatodendritic nAChRs in chick lumbar sympathetic ganglia include four nAChR subtypes distinguished on the basis of conductance and kinetic profile. Nanomolar PGE(2) applied to the extrapatch membrane differentially regulates opening probability (Po), frequency and the opening duration of each nAChR channel subtype in cell-attached patches. PGE(2) decreases the Po of the predominant nAChR subtype (36 pS) and significantly increases Po and open duration of the 23 pS subtype. The 23 pS subtype is gated by the alpha 7-selective agonist choline, and choline-gated currents are inhibited by alpha-bungarotoxin. To examine whether PGE(2) modulates nAChRs at synaptic sites, we studied the effects of PGE(2) on amplitude and decay of synaptic currents in visceral motoneuron-sympathetic neuron co-cultures. PGE(2) significantly decreases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), consistent with the predominant inhibition by PGE(2) of all but the 23 pS subtype. The time constant of mEPSCs at PGE(2)-treated synapses is prolonged, which is also consistent with an increased contribution of the longer open duration of the 23 pS nAChR subtype with PGE(2) treatment. To examine the presynaptic effect of PGE(2), nanomolar nicotine was used. Nicotine induces facilitation of synaptic transmission by increasing mEPSC frequency, an action thought to involve presynaptic, alpha 7-containing nAChRs. In the presence of PGE(2), nicotine-induced synaptic facilitation persists. Thus the net effect of PGE(2) is to alter the profile of nAChRs contributing to synaptic transmission from larger conductance, briefer opening channels to smaller conductance, longer opening events. This subtype-specific modulation of nAChRs by PGE(2) may provide a mechanism for selective activation and suppression of synaptic pathways mediated by different nAChR subtype(s) at both pre- and postsynaptic sites.
神经元烟碱型乙酰胆碱受体（nAChRs）的多样性可能是乙酰胆碱和尼古丁调节突触传递的一个重要因素。我们测试了前列腺素E2（PGE2）是否以亚型特异性方式调节突触后nAChRs，PGE2是中枢和外周神经系统中神经元兴奋性的调节剂，并研究了PGE2对烟碱传递的影响。鸡腰交感神经节中的体树突nAChRs包括四种基于电导和动力学特征区分的nAChR亚型。应用于膜片外膜的纳摩尔浓度的PGE2以不同方式调节细胞贴附膜片中每个nAChR通道亚型的开放概率（Po）、频率和开放持续时间。PGE2降低了主要nAChR亚型（36 pS）的Po，并显著增加了23 pS亚型的Po和开放持续时间。23 pS亚型由α7选择性激动剂胆碱门控，胆碱门控电流被α-银环蛇毒素抑制。为了研究PGE2是否在突触部位调节nAChRs，我们研究了PGE2对内脏运动神经元-交感神经元共培养物中突触电流幅度和衰减的影响。PGE2显著降低微小兴奋性突触后电流（mEPSCs）的幅度，这与PGE2对除23 pS亚型外所有亚型的主要抑制作用一致。PGE2处理的突触处mEPSCs的时间常数延长，这也与PGE2处理后23 pS nAChR亚型较长开放持续时间的贡献增加一致。为了研究PGE2的突触前效应，使用了纳摩尔浓度的尼古丁。尼古丁通过增加mEPSC频率诱导突触传递的易化，这种作用被认为涉及突触前含α7的nAChRs。在PGE2存在的情况下，尼古丁诱导的突触易化持续存在。因此，PGE2的净效应是改变参与突触传递的nAChRs的特征，从较大电导、较短开放通道变为较小电导、较长开放事件。PGE2对nAChRs的这种亚型特异性调节可能为在突触前和突触后部位选择性激活和抑制由不同nAChR亚型介导的突触通路提供一种机制。
