Gymnopoulos Marco, Cingolani Lorenzo A, Pedarzani Paola, Stocker Martin
Department of Molecular Biology of Neuronal Signals, Max Planck Institute for Experimental Medicine, 37075, Göttingen, Germany.
J Comp Neurol. 2014 Apr 1;522(5):1072-101. doi: 10.1002/cne.23466.
Early electrical activity and calcium influx regulate crucial aspects of neuronal development. Small-conductance calcium-activated potassium (SK) channels regulate action potential firing and shape calcium influx through feedback regulation in mature neurons. These functions, observed in the adult nervous system, make them ideal candidates to regulate activity- and calcium-dependent processes in neurodevelopment. However, to date little is known about the onset of expression and regions expressing SK channel subunits in the embryonic and postnatal development of the central nervous system (CNS). To allow studies on the contribution of SK channels to different phases of development of single neurons and networks, we have performed a detailed in situ hybridization mapping study, providing comprehensive distribution profiles of all three SK subunits (SK1, SK2, and SK3) in the rat CNS during embryonic and postnatal development. SK channel transcripts are expressed at early stages of prenatal CNS development. The three SK channel subunits display different developmental expression gradients in distinct CNS regions, with time points of expression and up- or downregulation that can be associated with a range of diverse developmental events. Their early expression in embryonic development suggests an involvement of SK channels in the regulation of developmental processes. Additionally, this study shows how the postnatal ontogenetic patterns lead to the adult expression map for each SK channel subunit and how their coexpression in the same regions or neurons varies throughout development.
早期电活动和钙内流调节神经元发育的关键方面。小电导钙激活钾（SK）通道在成熟神经元中通过反馈调节来调节动作电位发放并塑造钙内流。在成体神经系统中观察到的这些功能，使其成为调节神经发育中依赖活动和钙的过程的理想候选者。然而，迄今为止，关于中枢神经系统（CNS）胚胎期和出生后发育过程中SK通道亚基的表达起始和表达区域知之甚少。为了研究SK通道对单个神经元和神经网络不同发育阶段的贡献，我们进行了一项详细的原位杂交定位研究，提供了大鼠CNS在胚胎期和出生后发育过程中所有三种SK亚基（SK1、SK2和SK3）的全面分布图谱。SK通道转录本在产前CNS发育的早期阶段表达。三种SK通道亚基在不同的CNS区域呈现出不同的发育表达梯度，其表达时间点以及上调或下调与一系列不同的发育事件相关。它们在胚胎发育中的早期表达表明SK通道参与了发育过程的调节。此外，本研究展示了出生后的个体发育模式如何导致每个SK通道亚基的成体表达图谱，以及它们在同一区域或神经元中的共表达在整个发育过程中是如何变化的。
