Dept. of Neurology and Neurosurgery, McGill Univ., Montreal Neurological Institute, BT 110, 3801 Univ. St., Montreal, Quebec H3A 2B4, Canada.
J Neurophysiol. 2012 Jan;107(1):292-305. doi: 10.1152/jn.00767.2011. Epub 2011 Oct 12.
Expression of the 5-HT(1Apl(a)) receptor in Aplysia pleural sensory neurons inhibited 5-HT-mediated translocation of the novel PKC Apl II in sensory neurons and prevented PKC-dependent synaptic facilitation at sensory to motoneuron synapses (Nagakura et al. 2010). We now demonstrate that the ability of inhibitory receptors to block PKC activation is a general feature of inhibitory receptors and is found after expression of the 5-HT(1Apl(b)) receptor and with activation of endogenous dopamine and FMRFamide receptors in sensory neurons. Pleural sensory neurons are heterogeneous for their inhibitory response to endogenous transmitters, with dopamine being the most prevalent, followed by FMRFamide, and only a small number of neurons with inhibitory responses to 5-HT. The inhibitory response is dominant, reduces membrane excitability and synaptic efficacy, and can reverse 5-HT facilitation at both naive and depressed synapses. Indeed, dopamine can reverse PKC translocation during the continued application of 5-HT. Reversal of translocation can also be seen after translocation mediated by an analog of diacylglycerol, suggesting inhibition is not through blockade of diacylglycerol production. The effects of inhibition on PKC translocation can be rescued by phosphatidic acid, consistent with the inhibitory response involving a reduction or block of production of this lipid. However, phosphatidic acid could not recover PKC-dependent synaptic facilitation due to an additional inhibitory effect on the non-L-type calcium flux linked to synaptic transmission. In summary, we find a novel mechanism downstream of inhibitory receptors linked to inhibition of PKC activation in Aplysia sensory neurons.
5-HT(1Apl(a)) 受体在 Aplysia 胸膜感觉神经元中的表达抑制了 5-HT 介导的新型 PKC Apl II 在感觉神经元中的易位，并防止了 PKC 依赖性的感觉神经元到运动神经元突触的突触易化（Nagakura 等人，2010 年）。我们现在证明，抑制性受体阻断 PKC 激活的能力是抑制性受体的一个普遍特征，并且在表达 5-HT(1Apl(b)) 受体后以及在感觉神经元中激活内源性多巴胺和 FMRFamide 受体时可以发现。胸膜感觉神经元对其内源性递质的抑制反应具有异质性，其中多巴胺最为常见，其次是 FMRFamide，只有少数神经元对 5-HT 有抑制反应。抑制反应占主导地位，降低了膜兴奋性和突触效能，并且可以逆转未受影响和抑郁的突触的 5-HT 易化。事实上，多巴胺可以在持续应用 5-HT 的情况下逆转 PKC 易位。在二酰基甘油类似物介导的易位后也可以看到易位的逆转，这表明抑制不是通过阻断二酰基甘油的产生。抑制对 PKC 易位的影响可以通过磷脂酸挽救，这与抑制反应涉及减少或阻断这种脂质的产生一致。然而，由于对与突触传递相关的非 L 型钙通量的额外抑制作用，磷脂酸不能恢复 PKC 依赖性的突触易化。总之，我们在 Aplysia 感觉神经元中发现了一种与抑制 PKC 激活相关的新型抑制性受体下游机制。
