Bhattacharjee Arin, von Hehn Christian A A, Mei Xiaofeng, Kaczmarek Leonard K
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
J Comp Neurol. 2005 Mar 28;484(1):80-92. doi: 10.1002/cne.20462.
Na+-activated K+ currents (K(Na)) have been reported in multiple neuronal nuclei and the properties of K(Na) vary in different cell types. We have described previously the distribution of Slack, a Na+-activated K+ channel subunit. Another recently cloned Na+-activated K+ channel is Slick, which differs from Slack in its rapid activation and its sensitivity to intracellular ATP levels. We now report the localization of Slick in the rat central nervous system using in situ and immunohistochemical techniques. As for Slack, we find that Slick is widely distributed in the brain. Specifically, strong hybridization signals and immunoreactivity were found in the brainstem, including auditory neurons such as the medial nucleus of the trapezoid body. As has also been shown for Slack, Slick is expressed in the olfactory bulb, red nucleus, facial nucleus, pontine nucleus, oculomotor nucleus, substantia nigra, deep cerebellar nuclei, vestibular nucleus, and the thalamus. Slick mRNA and protein, however, also are found in certain neurons that do not express Slack. These neurons include those of the hippocampal CA1, CA2, and CA3 regions, the dentate gyrus, supraoptic nucleus, hypothalamus, and cortical layers II, III, and V. These data suggest that Slick may function independently of Slack in these regions. Computer simulations indicate that Slick currents can cause adaptation during prolonged stimuli. Such adaptation allows a neuron to respond to high-frequency stimulation with lower-frequency firing that remains temporally locked to individual stimuli, a property seen in many auditory neurons. Although it is not yet known if Slick and Slack subunits heteromultimerize, the existence of two genes that encode K(Na), that are widely expressed in the nervous system, with both overlapping and nonoverlapping distributions, provides the basis for the reported heterogeneity in the properties of K(Na) from various neurons.
钠激活钾电流（K(Na)）已在多个神经细胞核中被报道，并且K(Na)的特性在不同细胞类型中有所不同。我们之前已经描述了钠激活钾通道亚基Slack的分布。另一种最近克隆的钠激活钾通道是Slick，它在快速激活和对细胞内ATP水平的敏感性方面与Slack不同。我们现在使用原位和免疫组织化学技术报告Slick在大鼠中枢神经系统中的定位。与Slack一样，我们发现Slick在脑中广泛分布。具体而言，在脑干中发现了强烈的杂交信号和免疫反应性，包括梯形体内侧核等听觉神经元。正如Slack所显示的那样，Slick也在嗅球、红核、面神经核、脑桥核、动眼神经核、黑质、小脑深部核团、前庭核和丘脑中表达。然而，在某些不表达Slack的神经元中也发现了Slick mRNA和蛋白质。这些神经元包括海马CA1、CA2和CA3区、齿状回、视上核、下丘脑以及皮质层II、III和V的神经元。这些数据表明，Slick在这些区域可能独立于Slack发挥作用。计算机模拟表明，Slick电流可在长时间刺激期间引起适应性变化。这种适应性使神经元能够以较低频率的放电对高频刺激做出反应，且这种放电在时间上仍与单个刺激保持同步，这是许多听觉神经元所具有的特性。虽然尚不清楚Slick和Slack亚基是否形成异源多聚体，但在神经系统中广泛表达的两个编码K(Na)的基因的存在，其分布既有重叠又有非重叠，为报道的来自各种神经元的K(Na)特性的异质性提供了基础。
