Hori N, Galeno T, Carpenter D O
Cell Mol Neurobiol. 1987 Mar;7(1):73-90. doi: 10.1007/BF00734991.
The actions of ionophoretically applied N-methyl aspartate (NMA), quisqualate, and kainate, thought to activate three different types of excitatory amino acid receptors, were studied on pyramidal neurons of the rat pyriform cortex, maintained in an isolated, submerged, and perfused brain slice. Intracellular recordings were made with either K acetate or CsCl electrodes. In most neurons all three agonists elicited monophasic responses which could be evoked at 20-sec intervals. Some neurons showed biphasic responses, most commonly to kainate but, on occasion, also for quisqualate. The slower component appeared to be correlated with excitotoxicity and, consequently, was difficult to study. As a result the kainate responses studied were from neurons selected for having a single component. In neurons selected for having a linear current-voltage relationship or neurons loaded with Cs to suppress K conductance and linearize the current-voltage relationship, the average changes in resistance recorded during ionophoretic responses at resting potential were as follows: NMA, 131.2 +/- 6.7% of control; kainate, 104.7 +/- 5.8% of control; and quisqualate, 92.8 +/- 2.8% of control. The magnitude and direction of the conductance change were very reproducible in any one neuron, but especially for kainate some cells showed clear conductance increases, while others showed clear conductance decreases. Using CsCl electrodes it was possible to reduce K+ conductance and depolarize the neurons over a wider range. By passing depolarizing current it was possible to reverse the responses. The response to all three agonists reversed at the same depolarized potential. This observation indicates that while there are differences in the ionic channels associated with the three agonists at resting potential, the channels have similar properties at more depolarized potentials. Responses to all three agonists were influenced by the concentrations of divalent cations in the perfusion medium. The NMA responses were most sensitive to Mg, increasing in amplitude in the absence of Mg and being depressed by Mg elevation. All responses were sensitive to Ca, with discharges being greatly increased by low Ca and depressed by high Ca. The kainate response was most sensitive to Ca concentration changes. Unlike reports from other preparations the apparent conductance decreases to NMA were not altered by the perfusion of solutions with either no added Mg or no added Ca. The NMA response was very much reduced in either Co (1-2 mM) or Zn (100-200 microM).(ABSTRACT TRUNCATED AT 400 WORDS)
研究了离子电泳施加的N-甲基天冬氨酸（NMA）、quisqualate和海人藻酸的作用，这些物质被认为可激活三种不同类型的兴奋性氨基酸受体，研究对象是取自大鼠梨状皮质的锥体神经元，该神经元保存在分离、浸没并灌注的脑片中。使用醋酸钾或氯化铯电极进行细胞内记录。在大多数神经元中，所有这三种激动剂都引发单相反应，这种反应可每隔20秒诱发一次。一些神经元表现出双相反应，最常见于对海人藻酸，但偶尔对quisqualate也有双相反应。较慢的成分似乎与兴奋毒性相关，因此难以研究。结果，所研究的海人藻酸反应来自被选择为具有单一成分的神经元。在被选择为具有线性电流-电压关系的神经元或加载氯化铯以抑制钾电导并使电流-电压关系线性化的神经元中，在静息电位下离子电泳反应期间记录的电阻平均变化如下：NMA为对照的131.2±6.7%；海人藻酸为对照的104.7±5.8%；quisqualate为对照的92.8±2.8%。电导变化的幅度和方向在任何一个神经元中都非常可重复，但特别是对于海人藻酸，一些细胞显示出明显的电导增加，而另一些细胞则显示出明显的电导降低。使用氯化铯电极可以降低钾离子电导并在更宽的范围内使神经元去极化。通过施加去极化电流可以使反应逆转。对所有三种激动剂的反应在相同的去极化电位下逆转。这一观察结果表明，虽然在静息电位下与这三种激动剂相关的离子通道存在差异，但在更高的去极化电位下这些通道具有相似的特性。对所有三种激动剂的反应都受到灌注介质中二价阳离子浓度的影响。NMA反应对镁最为敏感，在无镁时幅度增加，而镁浓度升高则使其受到抑制。所有反应对钙都敏感，低钙时放电大大增加，高钙时则受到抑制。海人藻酸反应对钙浓度变化最为敏感。与其他制剂的报道不同，无论灌注不添加镁的溶液还是不添加钙的溶液，对NMA明显的电导降低均未改变。在钴（1 - 2 mM）或锌（100 - 200 microM）中，NMA反应都大大降低。（摘要截于400字）
