Tkatch T, Baranauskas G, Surmeier D J
Department of Physiology and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611, USA.
J Neurosci. 2000 Jan 15;20(2):579-88. doi: 10.1523/JNEUROSCI.20-02-00579.2000.
A-type K(+) currents are key determinants of repetitive activity and synaptic integration. Although several gene families have been shown to code for A-type channel subunits, recent studies have suggested that Kv4 family channels are the principal contributors to A-type channels in the somatodendritic membrane of mammalian brain neurons. If this hypothesis is correct, there should be a strong correlation between Kv4 family mRNA and A-type channel protein or aggregate channel currents. To test this hypothesis, quantitative single-cell reverse transcription-PCR analysis of Kv4 family mRNA was combined with voltage-clamp analysis of A-type K(+) currents in acutely isolated neurons. These studies revealed that Kv4.2 mRNA abundance was linearly related to A-type K(+) current amplitude in neostriatal medium spiny neurons and cholinergic interneurons, in globus pallidus neurons, and in basal forebrain cholinergic neurons. In contrast, there was not a significant correlation between estimates of Kv4.1 or Kv4.3 mRNA abundance and A-type K(+) current amplitudes. These results argue that Kv4.2 subunits are major constituents of somatodendritic A-type K(+) channels in these four types of neuron. In spite of this common structural feature, there were significant differences in the voltage dependence and kinetics of A-type currents in the cell types studied, suggesting that other determinants may create important functional differences between A-type K(+) currents.
A 型钾电流是重复活动和突触整合的关键决定因素。尽管已经证明有几个基因家族编码 A 型通道亚基,但最近的研究表明,Kv4 家族通道是哺乳动物脑神经元树突体膜中 A 型通道的主要贡献者。如果这一假设正确,那么 Kv4 家族 mRNA 与 A 型通道蛋白或总通道电流之间应该存在很强的相关性。为了验证这一假设,将 Kv4 家族 mRNA 的定量单细胞逆转录 -PCR 分析与急性分离神经元中 A 型钾电流的电压钳分析相结合。这些研究表明,在新纹状体中等棘状神经元、胆碱能中间神经元、苍白球神经元和基底前脑胆碱能神经元中,Kv4.2 mRNA 的丰度与 A 型钾电流幅度呈线性相关。相比之下,Kv4.1 或 Kv4.3 mRNA 丰度估计值与 A 型钾电流幅度之间没有显著相关性。这些结果表明,Kv4.2 亚基是这四种类型神经元树突体 A 型钾通道的主要组成部分。尽管有这种共同的结构特征,但在所研究的细胞类型中,A 型电流的电压依赖性和动力学存在显著差异,这表明其他决定因素可能导致 A 型钾电流之间产生重要的功能差异。