Noradrenaline Modulates the Membrane Potential and Holding Current of Medial Prefrontal Cortex Pyramidal Neurons via β(1)-Adrenergic Receptors and HCN Channels.
Noradrenaline Modulates the Membrane Potential and Holding Current of Medial Prefrontal Cortex Pyramidal Neurons via β(1)-Adrenergic Receptors and HCN Channels.
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DOI：
10.3389/fncel.2017.00341
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发表时间：
2017
影响因子：
5.3
通讯作者：
Szulczyk P
中科院分区：
文献类型：
--
作者：
Grzelka K;Kurowski P;Gawlak M;Szulczyk P
内侧前额叶皮层 (mPFC) 接收来自蓝斑的密集去甲肾上腺素能投射。 mPFC 锥体神经元的肾上腺素神经支配在生理学（控制记忆形成、注意力、工作记忆和认知行为）和病理生理学（注意力缺陷多动障碍、创伤后应激障碍、创伤性脑损伤后认知恶化、与成瘾相关的行为改变、阿尔茨海默病和抑郁症）中发挥着重要作用。本研究的目的是阐明肾上腺素受体介导的 V 层 mPFC 锥体神经元静息膜电位控制的机制。突触隔离的 V 层 mPFC 锥体神经元的膜电位或保持电流以穿孔贴片和经典全细胞配置的形式记录在年轻大鼠的切片中。去甲肾上腺素（NA）是一种对所有类型的肾上腺素能受体都有亲和力的神经递质，其应用会在测试的神经元中引起去极化或内向电流，无论记录是在穿孔贴片还是经典的全细胞配置中进行。去甲肾上腺素的作用取决于β1-肾上腺素能受体刺激，而不是α1-或α2-肾上腺素能受体刺激。 β1-肾上腺素能受体的激活通过超极化激活的环核苷酸门控 (HCN) 通道导致内向 Na+ 电流增加，该通道携带混合的 Na+/K+ 电流。蛋白激酶A和C、糖原合成酶激酶3β和酪氨酸激酶相关信号通路不参与β1肾上腺素能受体和HCN通道之间的信号转导。该转导系统以膜分隔方式运行，涉及 G 蛋白的 βγ 亚基。因此，去甲肾上腺素通过β1-肾上腺素能受体控制mPFC锥体神经元的静息膜电位和保持电流，进而通过涉及βγ亚基的信号通路激活HCN通道。
The medial prefrontal cortex (mPFC) receives dense noradrenergic projections from the locus coeruleus. Adrenergic innervation of mPFC pyramidal neurons plays an essential role in both physiology (control of memory formation, attention, working memory, and cognitive behavior) and pathophysiology (attention deficit hyperactivity disorder, posttraumatic stress disorder, cognitive deterioration after traumatic brain injury, behavioral changes related to addiction, Alzheimer’s disease and depression). The aim of this study was to elucidate the mechanism responsible for adrenergic receptor-mediated control of the resting membrane potential in layer V mPFC pyramidal neurons. The membrane potential or holding current of synaptically isolated layer V mPFC pyramidal neurons was recorded in perforated-patch and classical whole-cell configurations in slices from young rats. Application of noradrenaline (NA), a neurotransmitter with affinity for all types of adrenergic receptors, evoked depolarization or inward current in the tested neurons irrespective of whether the recordings were performed in the perforated-patch or classical whole-cell configuration. The effect of noradrenaline depended on β1- and not α1- or α2-adrenergic receptor stimulation. Activation of β1-adrenergic receptors led to an increase in inward Na+ current through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which carry a mixed Na+/K+ current. The protein kinase A- and C-, glycogen synthase kinase-3β- and tyrosine kinase-linked signaling pathways were not involved in the signal transduction between β1-adrenergic receptors and HCN channels. The transduction system operated in a membrane-delimited fashion and involved the βγ subunit of G-protein. Thus, noradrenaline controls the resting membrane potential and holding current in mPFC pyramidal neurons through β1-adrenergic receptors, which in turn activate HCN channels via a signaling pathway involving the βγ subunit.
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影响因子：
34.7
作者：
Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
影响因子：
2.5
作者：
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2.5
作者：
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作者：
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