Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
J Physiol. 2013 May 15;591(10):2509-21. doi: 10.1113/jphysiol.2012.248526. Epub 2013 Feb 25.
NMDA receptor-dependent, intrinsic membrane potential oscillations are an important element in the operation of the lamprey locomotor network. They involve a cyclic influx of calcium, leading to an activation of calcium-activated potassium (KCa) channels that in turn contributes to the termination of the depolarized plateau and membrane repolarization. In this study, we have investigated the calcium dynamics in different regions of lamprey spinal neurons during membrane potential oscillations, using confocal calcium imaging in combination with intracellular recordings. Calcium fluctuations were observed in both soma and dendrites, timed to the oscillations. The calcium level increased sharply at the onset of membrane depolarization, to reach its maximum by the end of the plateau. The calcium peak in distal dendrites typically occurred earlier than in the soma during the oscillatory cycle. The L-type calcium channel blocker nimodipine increased the duration of the depolarized plateau phase in most cells tested, whereas the agonist Bay K 8644 decreased plateau duration. Bay K 8644 increased the amplitude of calcium fluctuations, particularly in distal dendrites, whereas nimodipine caused a decrease, suggesting that L-type low-voltage-activated calcium channels are mainly localized in these regions. Our results thus indicate that dendritic CaV1.3-like calcium channels are activated during NMDA-mediated membrane potential oscillations. This calcium influx activates KCa channels involved in plateau termination.
NMDA 受体依赖性的内在膜电位振荡是文昌鱼运动网络运作的一个重要元素。它们涉及钙的循环内流，导致钙激活钾（KCa）通道的激活，进而有助于终止去极化平台和膜复极化。在这项研究中，我们使用共聚焦钙成像与细胞内记录相结合，研究了文昌鱼脊髓神经元在膜电位振荡过程中不同区域的钙动力学。在体和树突中都观察到了与振荡同步的钙波动。钙水平在膜去极化开始时急剧增加，在平台结束时达到最大值。在振荡周期中，远端树突中的钙峰通常比体部更早出现。在大多数测试的细胞中，L 型钙通道阻滞剂尼莫地平增加了去极化平台期的持续时间，而激动剂 Bay K 8644 则缩短了平台期。Bay K 8644 增加了钙波动的幅度，特别是在远端树突中，而尼莫地平则导致其降低，表明 L 型低电压激活钙通道主要定位于这些区域。因此，我们的结果表明，在 NMDA 介导的膜电位振荡过程中，树突状 CaV1.3 样钙通道被激活。这种钙内流激活了参与平台终止的 KCa 通道。
