Bengtson C Peter, Kaiser Martin, Obermayer Joshua, Bading Hilmar
Department of Neurobiology, University of Heidelberg, Heidelberg, Germany.
Biochim Biophys Acta. 2013 Jul;1833(7):1672-9. doi: 10.1016/j.bbamcr.2013.01.022. Epub 2013 Jan 27.
Both synaptic N-methyl-d-aspartate (NMDA) receptors and voltage-operated calcium channels (VOCCs) have been shown to be critical for nuclear calcium signals associated with transcriptional responses to bursts of synaptic input. However the direct contribution to nuclear calcium signals from calcium influx through NMDA receptors and VOCCs has been obscured by their concurrent roles in action potential generation and synaptic transmission. Here we compare calcium responses to synaptically induced bursts of action potentials with identical bursts devoid of any synaptic contribution generated using the pre-recorded burst as the voltage clamp command input to replay the burst in the presence of blockers of action potentials or ionotropic glutamate receptors. Synapse independent replays of bursts produced nuclear calcium responses with amplitudes around 70% of their original synaptically generated signals and were abolished by the L-type VOCC blocker, verapamil. These results identify a major direct source of nuclear calcium from local L-type VOCCs whose activation is boosted by NMDA receptor dependent depolarization. The residual component of synaptically induced nuclear calcium signals which was both VOCC independent and NMDA receptor dependent showed delayed kinetics consistent with a more distal source such as synaptic NMDA receptors or internal stores. The dual requirement of NMDA receptors and L-type VOCCs for synaptic activity-induced nuclear calcium dependent transcriptional responses most likely reflects a direct somatic calcium influx from VOCCs whose activation is amplified by synaptic NMDA receptor-mediated depolarization and whose calcium signal is boosted by a delayed input from distal calcium sources mostly likely entry through NMDA receptors and release from internal stores. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.
突触 N-甲基-D-天冬氨酸（NMDA）受体和电压门控钙通道（VOCCs）已被证明对于与突触输入爆发的转录反应相关的核钙信号至关重要。然而，通过 NMDA 受体和 VOCCs 的钙内流对核钙信号的直接贡献，因其在动作电位产生和突触传递中的并发作用而被掩盖。在这里，我们将对突触诱导的动作电位爆发的钙反应与使用预先记录的爆发作为电压钳制命令输入在存在动作电位阻滞剂或离子型谷氨酸受体阻滞剂的情况下重放爆发所产生的无任何突触贡献的相同爆发进行比较。突触独立的爆发重放产生的核钙反应幅度约为其原始突触产生信号的 70%，并被 L 型 VOCC 阻滞剂维拉帕米消除。这些结果确定了来自局部 L 型 VOCCs 的核钙的主要直接来源，其激活因 NMDA 受体依赖性去极化而增强。突触诱导的核钙信号的残余成分既不依赖于 VOCCs 也不依赖于 NMDA 受体，其动力学延迟，这与更远处的来源如突触 NMDA 受体或内部储存一致。NMDA 受体和 L 型 VOCCs 对突触活动诱导的核钙依赖性转录反应的双重需求很可能反映了来自 VOCCs 的直接体细胞钙内流，其激活因突触 NMDA 受体介导的去极化而放大，并且其钙信号因来自远处钙源的延迟输入（最有可能通过 NMDA 受体进入并从内部储存释放）而增强。本文是名为：第 12 届欧洲钙研讨会的特刊的一部分。
