DOPAMINE ENHANCES BOTH ELECTROTONIC COUPLING AND CHEMICAL EXCITATORY POSTSYNAPTIC POTENTIALS AT MIXED SYNAPSES
DOPAMINE ENHANCES BOTH ELECTROTONIC COUPLING AND CHEMICAL EXCITATORY POSTSYNAPTIC POTENTIALS AT MIXED SYNAPSES
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DOI：
10.1073/pnas.89.24.12088
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发表时间：
1992-12-15
影响因子：
11.1
通讯作者：
FABER, DS
中科院分区：
文献类型：
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作者：
PEREDA, A;TRILLER, A;FABER, DS
多巴胺递质减少了视网膜水平细胞之间的电紧张性耦合，并增加了它们对谷氨酸的敏感性。由于在其他系统中，单个传入与其靶点建立混合的电紧张性和化学兴奋性突触，多巴胺可能会抑制其中一个兴奋成分，同时增强另一个成分。通过在金鱼毛特纳细胞(M细胞)的外侧树突附近局部应用多巴胺，并监测刺激同侧第八神经诱发的复合电紧张性和化学兴奋性突触后电位和电流，验证了这一假说。多巴胺能持续增强突触后反应的两个组成部分，同时也增加了输入电导。所有这些多巴胺作用都是通过向大脑灌流含有多巴胺D1受体拮抗剂SCH-23390的生理盐水来阻止的。突触后注射cAMP依赖的蛋白激酶抑制剂(Walsh抑制剂，或PKI5-24)可阻断多巴胺诱导的突触传递变化，这暗示了cAMP依赖的机制。此外，M细胞有多巴胺能神经支配，免疫组织化学抗多巴胺抗体及其合成途径中的限速酶酪氨酸羟基酶证明了这一点。曲张免疫反应纤维位于建立混合突触的大的有髓俱乐部末梢之间的外侧树突的远侧部分附近。根据电子显微镜观察，多巴胺能纤维含有小的小泡，它们与传入细胞或M细胞都没有突触接触，而是留在突触床上。综上所述，这些结果表明，在距离这些终末较远的地方释放多巴胺，很可能是通过磷酸化机制，增加了这种初级感觉输入到M细胞的增益。
The transmitter dopamine reduces electrotonic coupling between retinal horizontal cell and increases their sensitivity to glutamate. Since in other systems single afferents establish mixed electrotonic and chemical excitatory synapses with their targets, dopamine might be expected there to depress one component of excitation while enhancing the other. This hypothesis was tested by applying dopamine locally in the vicinity of the lateral dendrite of the goldfish Mauthner cell (M cell) and monitoring the composite electrotonic and chemical excitatory postsynaptic potentials and currents evoked by ipsilateral eighth nerve stimulation. Dopamine produces persistent enhancements of both components of the postsynaptic response while it also increases input conductance. All these dopamine actions are prevented by superfusing the brain with saline containing the dopamine D1 receptor antagonist SCH-23390. Postsynaptic injections of the cAMP-dependent protein kinase inhibitor (Walsh inhibitor, or PKI5-24) block the dopamine-induced changes in synaptic transmission, implicating a cAMP-dependent mechanism. Furthermore, there is a dopaminergic innervation of the M cell, as demonstrated immunohistochemically with antibodies against dopamine and the rate-limiting enzyme in its synthetic pathway, tyrosine hydroxylase. Varicose immunoreactive fibers lie in the vicinity of the distal part of the lateral dendrite between the large myelinated club endings that establish the mixed synapses. As determined with electron microscopy, the dopaminergic fibers contain small vesicles, and they do not have synaptic contacts with either the afferents or the M cell, remaining instead in the synaptic bed. Taken together, these results suggest that dopamine released at a distance from these terminals increases the gain of this primary sensory input to the M cell, most likely through a phosphorylation mechanism.