Wang X, Gruenstein E I
Neuroscience Graduate Program, University of Cincinnati College of Medicine, OH 45267-0524, USA.
Brain Res. 1997 Sep 5;767(2):239-49. doi: 10.1016/s0006-8993(97)00585-4.
Dissociated rat cortical neurons reassociate in vitro to form synaptically connected networks. Removal of Mg2+ from the extracellular medium then induces neurons in the network to undergo synchronized oscillations of cytoplasmic calcium. Previous studies have shown that these calcium oscillations involve the activation of NMDA receptors and that the rising phase of each calcium spike is coincident with a brief burst of action potentials (Robinson et al., Jpn. J. Physiol. 43 (Suppl. 1) (1993) S125-130; Robinson et al., J. Neurophysiol. 70 (1993) 1606-1616; Murphy et al., J. Neurosci. 12 (1992) 4834-4845). We have found that these calcium oscillations are dependent on an influx of extracellular calcium but are independent of mobilization of calcium from intracellular stores. The influx of extracellular Ca2+ occurs primarily through L-type voltage-gated calcium channels (VGCCs), since diltiazem inhibits calcium oscillations under all conditions. On the other hand, N-, P/Q-, and T-type VGCCs are not required for calcium oscillations, although inhibitors of these channels may act as partial antagonists. In addition to removal of Mg2+, oscillations can also be induced by the inhibition of voltage-gated K+ channels with 4-aminopyridine (4-AP), a treatment known to increase neurotransmitter release. In the presence of 4-AP, synchronized calcium oscillations become independent of NMDA receptor activation, although they continue to require activation of AMPA/KA receptors. A model for the mechanism of neuronal calcium oscillations and the reason for their synchrony is presented.
解离的大鼠皮层神经元在体外重新结合形成突触连接网络。从细胞外培养基中去除Mg2+会诱导网络中的神经元发生细胞质钙的同步振荡。先前的研究表明，这些钙振荡涉及NMDA受体的激活，并且每个钙峰的上升阶段与短暂的动作电位爆发同时发生（Robinson等人，《日本生理学杂志》43（增刊1）（1993年）S125 - 130；Robinson等人，《神经生理学杂志》70（1993年）1606 - 1616；Murphy等人，《神经科学杂志》12（1992年）4834 - 4845）。我们发现这些钙振荡依赖于细胞外钙的内流，但与细胞内钙库中钙的动员无关。细胞外Ca2+的内流主要通过L型电压门控钙通道（VGCCs）发生，因为地尔硫䓬在所有条件下都能抑制钙振荡。另一方面，N型、P/Q型和T型VGCCs对于钙振荡不是必需的，尽管这些通道的抑制剂可能作为部分拮抗剂起作用。除了去除Mg2+之外，用4 - 氨基吡啶（4 - AP）抑制电压门控K+通道也可以诱导振荡，4 - AP这种处理已知会增加神经递质释放。在4 - AP存在的情况下，同步钙振荡变得独立于NMDA受体激活，尽管它们仍然需要AMPA/KA受体的激活。本文提出了神经元钙振荡机制及其同步性原因的模型。
