Maletic-Savatic M, Lenn N J, Trimmer J S
Department of Neurology, State University of New York, Stony Brook, New York 11794, USA.
J Neurosci. 1995 May;15(5 Pt 2):3840-51. doi: 10.1523/JNEUROSCI.15-05-03840.1995.
Hippocampal neurons are highly plastic in their excitable properties, both during development and in the adult brain. As voltage-sensitive K+ channels are major determinants of membrane excitability, one mechanism for generating plasticity is through regulation of K+ channel activity. To gain insights into the regulation of K+ channels in the hippocampus, we have analyzed the spatiotemporal expression patterns of five K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro. Delayed rectifier-type channels (Kv1.5, Kv2.1, and Kv2.2) are expressed on all neuronal somata and proximal dendrites, while A-type channels (Kv1.4 and Kv4.2) are present distally on distinct subpopulations of neurons. The development of these patterns in situ is monotonic; that is, while the time and spatial development varies among the channels, each K+ channel subtype initially appears in its adult pattern, suggesting that the mechanisms underlying spatial patterning operate through development. Immunoblots confirm the differential temporal expression of K+ channels in the developing hippocampus, and demonstrate developmentally regulated changes in the microheterogeneity of some K+ channel polypeptide species. Temporal expression patterns of all five K+ channels observed in situ are retained in vitro, while certain aspects of cellular and subcellular localization are altered for some of the K+ channel polypeptides studied. Similarities in K+ channel polypeptide expression in situ and in vitro indicate that the same regulatory mechanisms are controlling spatiotemporal patterning in both situations. However, differences between levels of expression for all subtypes studied except Kv2.1 indicate additional mechanisms operating in situ but absent in vitro that are important in determining polypeptide abundance.
海马神经元在发育过程中和成年大脑中,其兴奋性特性具有高度可塑性。由于电压敏感性钾离子通道是膜兴奋性的主要决定因素,产生可塑性的一种机制是通过调节钾离子通道活性。为了深入了解海马体中钾离子通道的调节机制,我们分析了五种钾离子通道多肽在原位和体外发育的大鼠海马神经元中的时空表达模式。延迟整流型通道(Kv1.5、Kv2.1和Kv2.2)在所有神经元胞体和近端树突上表达,而A型通道(Kv1.4和Kv4.2)则存在于神经元不同亚群的远端。这些模式在原位的发育是单调的;也就是说,虽然各通道的时间和空间发育有所不同,但每种钾离子通道亚型最初都以其成年模式出现,这表明空间模式形成的机制在发育过程中起作用。免疫印迹证实了发育中的海马体中钾离子通道的差异时间表达,并证明了一些钾离子通道多肽种类的微异质性在发育过程中受到调节的变化。在原位观察到的所有五种钾离子通道的时间表达模式在体外得以保留,而所研究的一些钾离子通道多肽的细胞和亚细胞定位的某些方面发生了改变。原位和体外钾离子通道多肽表达的相似性表明,相同的调节机制在两种情况下都控制着时空模式形成。然而,除Kv2.1外,所有研究亚型的表达水平之间的差异表明,原位存在但体外不存在的其他机制在决定多肽丰度方面很重要。