Weiler R, Schultz K, Janssen-Bienhold U
Department of Neurobiology, University of Oldenburg, Germany.
Eur J Neurosci. 1995 Sep 1;7(9):1914-9. doi: 10.1111/j.1460-9568.1995.tb00713.x.
The formation of spinules at the terminal dendrites of retinal horizontal cells with the onset of light and their subsequent retraction during darkness is a remarkable example of synaptic plasticity where sensory experience modifies reversibly, and on a time scale of minutes the ultrastructure of synaptic connectivity. The signals and the subsequent intracellular cascades underlying the prominent morphological alterations are only partially understood. We show here that lowering the external calcium concentration did prevent dark- and AMPA-induced retraction of spinules in a eyecup preparation. Furthermore, spinule retraction was prevented in vivo by the injection of calmidazolium, an inhibitor of calmodulin, into the eyeball, and also by the injection of KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinase (CaMkII). We conclude that local Ca2+ influx through AMPA-gated channels followed by activation of CaMkII is an important step for spinule retraction during dark adaptation. The phosphorylation patterns of phosphoproteins derived from purified horizontal cells was affected by the inhibitors of calmodulin and CaMkII respectively. Some of the affected phosphoproteins appeared to be cytoskeleton-associated proteins, including GAP-43. Based on these observations, a putative scenario for the retraction of spinules is proposed.
随着光照开始,视网膜水平细胞终末树突上会形成棘状小体,而在黑暗期间这些棘状小体随后会回缩,这是突触可塑性的一个显著例子,即感觉经验可在数分钟的时间尺度上对突触连接的超微结构进行可逆性修饰。导致这种显著形态改变的信号及随后的细胞内级联反应仅得到部分理解。我们在此表明,降低细胞外钙浓度确实能在眼杯制备中阻止黑暗和AMPA诱导的棘状小体回缩。此外,通过向眼球内注射钙调蛋白抑制剂 calmidazolium 以及注射 Ca2+/钙调蛋白依赖性蛋白激酶(CaMkII)抑制剂 KN-62,可在体内阻止棘状小体回缩。我们得出结论,通过AMPA门控通道的局部Ca2+内流,随后激活CaMkII,是暗适应期间棘状小体回缩的重要步骤。分别来自纯化水平细胞的磷蛋白的磷酸化模式受到钙调蛋白和CaMkII抑制剂的影响。一些受影响的磷蛋白似乎是细胞骨架相关蛋白,包括GAP-43。基于这些观察结果,提出了一个关于棘状小体回缩的推测情况。