Do canonical transient receptor potential channels mediate cholinergic excitation of cortical pyramidal neurons?
Do canonical transient receptor potential channels mediate cholinergic excitation of cortical pyramidal neurons?
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DOI：
10.1097/wnr.0b013e3283621344
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发表时间：
2013-07-10
期刊：
影响因子：
1.7
通讯作者：
Gulledge, Allan T.
中科院分区：
文献类型：
--
作者：
Dasari, Sameera;Abramowitz, Joel;Gulledge, Allan T.
M1型毒蕈碱型乙酰胆碱受体的激活激活新皮层锥体神经元，部分通过门控非选择性阳离子电导，在短的动作电位序列后产生钙依赖性后去极化电位（ADP）。尽管介导ADP的阳离子电导的身份尚不清楚，但之前的工作涉及典型的瞬时受体电位（TRPC）通道，特别是TRPC 5和TRPC 6亚型。使用药理学和遗传学的方法，我们测试的作用TRPC通道产生胆碱能ADP在第5层锥体神经元在小鼠内侧前额叶皮层（mPFC）。各种阻断TRPC通道的化合物，包括2-氨基乙氧基二苯基硼酸盐、氟灭酸、镧、SKF-96365和Pyr-3，对胆碱能ADP几乎没有影响。类似地，几个TRPC亚基的基因缺失，包括TRC 1、TRPC 5和TRPC 6（单敲除），或TRPC 5和TRPC 6一起（双敲除），未能降低胆碱能ADP的幅度。这些数据表明，TRPC 5和TRPC 6亚基不需要胆碱能兴奋的第5层锥体神经元在小鼠mPFC和未来的工作重点应扩大到测试其他潜在的离子效应器的参与。(C)2013年威科健康垂直酒吧利平科特威廉姆斯&威尔金斯。
Activation of M1-type muscarinic acetylcholine receptors excites neocortical pyramidal neurons, in part by gating a nonselective cation conductance that produces calcium-dependent afterdepolarizing potentials' (ADPs) following short trains of action potentials. Although the identity of the cation conductance mediating the ADP is not known, previous work has implicated canonical transient receptor potential (TRPC) channels, specifically the TRPC5 and TRPC6 subtypes. Using pharmacological and genetic approaches, we tested the role of TRPC channels in generating cholinergic ADPs in layer 5 pyramidal neurons in the mouse medial prefrontal cortex (mPFC). A variety of compounds that block TRPC channels, including 2-aminoethoxydiphenyl borate, flufenamic acid, lanthanum, SKF-96365, and Pyr-3, had little, if any, impact on cholinergic ADPs. Similarly, genetic deletion of several TRPC subunits, including TPRC1, TRPC5, and TRPC6 (single knockouts), or both TRPC5 and TRPC6 together (double knockout), failed to reduce the amplitude of cholinergic ADPs. These data suggest that TRPC5 and TRPC6 subunits are not required for cholinergic excitation of layer 5 pyramidal neurons in the mouse mPFC and that the focus of future work should be expanded to test the involvement of other potential ionic effectors. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.