Presynaptic α2-adrenoceptors control excitatory, but not inhibitory, transmission at rat hippocampal synapses
Presynaptic α2-adrenoceptors control excitatory, but not inhibitory, transmission at rat hippocampal synapses
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DOI：
10.1111/j.1469-7793.1999.0439m.x
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发表时间：
1999-09-01
影响因子：
5.5
通讯作者：
Boehm, S
中科院分区：
文献类型：
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作者：
Boehm, S
1. 通过记录神经胶质微岛上分离的单个神经元的自动电流，研究去甲肾上腺素对大鼠海马突触神经传递的影响。去甲肾上腺素以百日咳毒素敏感的方式减少兴奋性而非抑制性自动电流，但胺不影响谷氨酸诱发的电流。2．去甲肾上腺素对兴奋性自动电流的抑制在 0.11 +/- 0.06 μM 时达到半最大。α(2)-肾上腺素受体激动剂 UK 14 304 和可乐定在降低这些电流方面与去甲肾上腺素等效，而 α(1)-肾上腺素受体激动剂甲氧胺和 β-肾上腺素受体激动剂 异丙肾上腺素（isoproterenol）无效。去甲肾上腺素对兴奋性自动电流的减少不被α(1)-肾上腺素能拮抗剂乌拉地尔或β-拮抗剂普萘洛尔改变，但被α(2)-拮抗剂育亨宾减少。亚型偏好拮抗剂萝芙辛和酚妥拉明（均为 0.3 μM）分别引起去甲肾上腺素依赖性兴奋性自动突触电流减少的浓度-反应曲线向右移动 9 倍和 36 倍。哌唑嗪(1μM)不影响该浓度-反应曲线。3．去甲肾上腺素可减少兴奋性微岛神经元中电压激活的 Ca2+ 电流，但不会减少抑制性微岛神经元中的电压激活 Ca2+ 电流。相比之下，GABA(B) 激动剂巴氯芬减少了两种神经元的兴奋性和抑制性自动电流，并减少了电压激活的 Ca2+ 电流。去甲肾上腺素对 Ca2+ 电流的抑制在 0.17 +/- 0.05 μM 时达到半最大，UK 14304 和可乐定在降低这些电流方面与去甲肾上腺素等效。去甲肾上腺素引起的 Ca2+ 电流减少可被育亨宾拮抗，但乌拉地尔或普萘洛尔则不能拮抗。亚型偏好的α(2)-肾上腺素能拮抗剂的活性顺序如下：酚妥拉明>萝沃尔辛>哌唑嗪。4．去甲肾上腺素不影响K+电流，也不能改变海马神经元大量培养物中测量的微型兴奋性突触后电流的频率。5．这些结果表明，去甲肾上腺素通过α(2A/D)亚型的突触前α(2)-肾上腺素能受体调节谷氨酸能海马突触的传递，但不调节GABA能海马突触的传递。这种抑制作用涉及抑制电压激活的 Ca2+ 电流，但不调节自发的囊泡胞吐作用或电压激活的 K+ 电流。
1. The effects of noradrenaline on neurotransmission at rat hippocampal synapses were investigated by recording autaptic currents in single neurons isolated on glial microislands. Noradrenaline reduced excitatory, but not inhibitory, autaptic currents in a pertussis toxin-sensitive manner, but the amine did not affect glutamate-evoked currents.2. The inhibition of excitatory autaptic currents by noradrenaline was half-maximal at 0.11 +/- 0.06 mu M. The alpha(2)-adrenoceptor agonists UK 14 304 and clonidine were equipotent to noradrenaline in reducing these currents, whereas the alpha(1)-adrenoceptor agonist methoxamine and the beta-adrenoceptor agonist isoprenaline (isoproterenol) were ineffective. The reduction of excitatory autaptic currents by noradrenaline was not altered by the alpha(1)-adrenergic antagonist urapidil or the beta-antagonist propranolol, but reduced by the alpha(2)-antagonist yohimbine. The subtype-preferring antagonists rauwolscine and phentolamine (both at 0.3 mu M) caused 9-fold and 36-fold rightward shifts in the concentration-response curve for the noradrenaline-dependent reduction of excitatory autaptic currents, respectively. Prazosine (1 mu M) did not affect this concentration-response curve.3. Noradrenaline reduced voltage-activated Ca2+ currents in excitatory, but not in inhibitory, microisland neurons. For comparison, the GABA(B) agonist baclofen reduced both excitatory and inhibitory autaptic currents and diminished voltage-activated Ca2+ currents in both types of neurons. The inhibition of Ca2+ currents by noradrenaline was half-maximal at 0.17 +/- 0.05 mu M, and UK 14304 and clonidine were equipotent to noradrenaline in reducing these currents. The noradrenaline-induced reduction of Ca2+ currents was antagonized by yohimbine, but not by urapidil or propranolol; the subtype-preferring alpha(2)-adrenergic antagonists displayed the following rank order of activity: phentolamine > rauwolscine > prazosine.4. Noradrenaline did not affect K+ currents and failed to alter the frequency of miniature excitatory postsynaptic currents measured in mass cultures of hippocampal neurons.5. These results show that noradrenaline regulates transmission at glutamatergic, but not at GABAergic, hippocampal synapses via presynaptic alpha(2)-adrenoceptors of the alpha(2A/D) subtype. This inhibitory action involves an inhibition of voltage-activated Ca2+ currents, but no modulation of spontaneous vesicle exocytosis or of voltage-activated K+ currents.