Robust pacemaking in substantia nigra dopaminergic neurons.
Robust pacemaking in substantia nigra dopaminergic neurons.
复制标题
DOI：
10.1523/jneurosci.2519-09.2009
复制
发表时间：
2009-09-02
期刊：
影响因子：
--
通讯作者：
Surmeier DJ
中科院分区：
文献类型：
--
作者：
Guzman JN;Sánchez-Padilla J;Chan CS;Surmeier DJ
黑质致密部的多巴胺能神经元是自主起搏器。这种活动负责多巴胺的持续释放，这是纹状体等靶结构正常运作所必需的。体树突状L型钙通道长期以来一直被认为对这种活动很重要，如果不是必要的话。这里报道的研究挑战了这一观点。在脑片上采用光和电生理相结合的方法，发现拮抗L型钙通道有效地阻止树突状钙振荡，但不改变自主起搏。此外，用外源性缓冲液抑制细胞内钙振荡对起搏频率影响不大。虽然不是起搏所必需的，但当受到阳离子通道阻滞剂的挑战时，L类型的通道有助于支持起搏。模拟结果表明，L类通道对拮抗的不敏感性反映了起搏过程的多通道特性。起搏的健壮性强调了它的生物学重要性，并为理解针对L型钙通道的疗法如何在不损害功能的情况下保护帕金森病中的多巴胺能神经元提供了一个框架。
Dopaminergic neurons of the substantia nigra pars compacta are autonomous pacemakers. This activity is responsible for the sustained release of dopamine necessary for the proper functioning of target structures like the striatum. Somatodendritic L-type Ca2+ channels have long been viewed as important, if not necessary, for this activity. The studies reported here challenge this viewpoint. Using a combination of optical and electrophysiological approaches in brain slices, it was found that antagonism of L-type Ca2+ channel effectively stopped dendritic Ca2+ oscillations, but left autonomous pacemaking unchanged. Moreover, damping intracellular Ca2+ oscillations with exogenous buffer had little effect on pacemaking rate. Although not necessary for pacemaking, L-type channels helped support pacemaking when challenged with cationic channel blockers. Simulations suggested that the insensitivity to antagonism of L-type channels reflected the multichannel nature of the pacemaking process. The robustness of pacemaking underscores its biological importance and provides a framework for understanding how therapeutics targeting L-type Ca2+ channels might protect dopaminergic neurons in Parkinson's disease without compromising their function.