L-type calcium channel agonist induces correlated depolarizations in mice lacking the beta2 subunit nAChRs.
L-type calcium channel agonist induces correlated depolarizations in mice lacking the beta2 subunit nAChRs.
复制标题
L 型钙通道激动剂在缺乏 β2 亚基 nAChR 的小鼠中诱导相关去极化。
作者：
C. Torborg;Chih;Gianna Muir;M. Feller
视网膜波部分由含有β 2亚单位的烟碱受体的激活介导。含有nAChR的β 2缺陷小鼠维持动作电位的放电，但不支持相关波。因此，β 2-/-小鼠抑制了视网膜内回路的细化以及视网膜向CNS的投射。以前，我们观察到，通过药理学应用L型钙通道激动剂FPL-64176，可以在β 2-/-视网膜中诱导与视网膜波相关的钙增加。在这里，我们使用全细胞和多电极阵列记录来表征FPL诱导的β 2-/-视网膜活动模式。FPL诱导先前非尖峰β 2-/-视网膜神经节细胞的强去极化。尽管这些强去极化可能是FPL诱导的钙瞬变的基础，但它们对单个视网膜神经节细胞的尖峰产生高度可变的影响。此外，诱导的尖峰活动具有比WT小鼠显著更弱的最近邻相关性。在β 2-/-小鼠中眼内注射FPL的初始尝试没有挽救眼睛特异性层形成。这些发现表明FPL诱导的活性不足以驱动β 2-/-小鼠中的眼特异性分离。
Retinal waves are mediated in part by activation of nicotinic receptors containing the beta2 subunit. Mice deficient in beta2 containing nAChRs have maintained firing of action potentials but do not support correlated waves. As a result, beta2-/- mice have inhibited refinement of circuits within the retina as well as retinal projections to the CNS. Previously, we observed that correlated increases in calcium reminiscent of retinal waves could be induced in beta2-/- retina by pharmacological application of the L-type calcium channel agonist, FPL-64176. Here, we characterize FPL-induced activity patterns in beta2-/- retina using both whole cell and multielectrode array recordings. FPL-induced strong depolarizations in previously non-spiking beta2-/- retinal ganglion cells. Though these strong depolarizations were likely to underlie the FPL-induced calcium transients, they led to highly variable effects on the spiking of individual retinal ganglion cells. In addition, induced spiking activity had significantly weaker nearest-neighbor correlations than WT mice. Initial attempts of intraocular injections of FPL in beta2-/- mice did not rescue eye-specific layer formation. These findings indicate that activity induced by FPL is not sufficient for driving eye-specific segregation in beta2-/- mice.