Tabarean Iustin V
The Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California, United States of America.
PLoS One. 2014 May 5;9(5):e96643. doi: 10.1371/journal.pone.0096643. eCollection 2014.
The electrogenic machinery of an excitable cell can adapt in response to changes in input, genetic deficit or in pathological conditions, however the underlying molecular mechanisms are not understood. In cases of genetic deletion it is commonly observed that a channel subunit from the same family replaces the missing one. We have previously reported that Kv4.2-/- preoptic GABAergic neurons display identical firing characteristics to those of wild-type neurons despite having reduced A-type currents, and that, surprisingly, they present a robust upregulation of a delayed rectifier current, the nature of which is unknown. Here, using pharmacology, qPCR and Western blots we report that, although the wild-type neurons express several Kv subunits, the upregulated current is conducted by the Kv1.5 subunit exclusively. Thus, this study reveals the molecular nature of a novel mechanism of electrical remodeling in central neurons.
可兴奋细胞的电活动机制能够根据输入、基因缺陷或病理状况的变化进行适应性调整,然而其潜在的分子机制仍不清楚。在基因缺失的情况下,通常会观察到来自同一家族的通道亚基替代了缺失的亚基。我们之前曾报道,尽管视前区GABA能神经元Kv4.2基因敲除后A型电流减少,但其放电特性与野生型神经元相同,而且令人惊讶的是,它们呈现出一种延迟整流电流的强劲上调,其性质尚不清楚。在此,我们运用药理学、定量聚合酶链反应(qPCR)和蛋白质免疫印迹法(Western blots)报告称,虽然野生型神经元表达多种Kv亚基,但上调的电流仅由Kv1.5亚基传导。因此,本研究揭示了中枢神经元电重塑新机制的分子本质。