Peng I-Feng, Wu Chun-Fang
Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, USA.
J Neurophysiol. 2007 Jan;97(1):780-94. doi: 10.1152/jn.01012.2006. Epub 2006 Nov 1.
Different K(+) currents participate in generating neuronal firing patterns. The Drosophila embryonic "giant" neuron culture system has facilitated current- and voltage-clamp recordings to correlate distinct excitability patterns with the underlying K(+) currents and to delineate the mutational effects of identified K(+) channels. Mutations of Sh and Shab K(+) channels removed part of inactivating I(A) and sustained I(K), respectively, and the remaining I(A) and I(K) revealed the properties of their counterparts, e.g., Shal and Shaw channels. Neuronal subsets displaying the delayed, tonic, adaptive, and damping spike patterns were characterized by different profiles of K(+) current voltage dependence and kinetics and by differential mutational effects. Shab channels regulated membrane repolarization and repetitive firing over hundreds of milliseconds, and Shab neurons showed a gradual decline in repolarization during current injection and their spike activities became limited to high-frequency, damping firing. In contrast, Sh channels acted on events within tens of milliseconds, and Sh mutations broadened spikes and reduced firing rates without eliminating any categories of firing patterns. However, removing both Sh and Shal I(A) by 4-aminopyridine converted the delayed to damping firing pattern, demonstrating their actions in regulating spike initiation. Specific blockade of Shab I(K) by quinidine mimicked the Shab phenotypes and converted tonic firing to a damping pattern. These conversions suggest a hierarchy of complexity in K(+) current interactions underlying different firing patterns. Different lineage-defined neuronal subsets, identifiable by employing the GAL4-UAS system, displayed different profiles of spike properties and K(+) current compositions, providing opportunities for mutational analysis in functionally specialized neurons.
不同的钾离子电流参与产生神经元放电模式。果蝇胚胎“巨型”神经元培养系统有助于进行电流钳和电压钳记录，以将不同的兴奋性模式与潜在的钾离子电流相关联，并描绘已鉴定钾离子通道的突变效应。Sh和Shab钾离子通道的突变分别去除了部分失活的I(A)和持续性I(K)，剩余的I(A)和I(K)揭示了它们对应通道（如Shal和Shaw通道）的特性。表现出延迟、强直、适应性和阻尼尖峰模式的神经元亚群具有不同的钾离子电流电压依赖性和动力学特征以及不同的突变效应。Shab通道在数百毫秒内调节膜复极化和重复放电，Shab神经元在电流注入期间复极化逐渐下降，其尖峰活动仅限于高频、阻尼放电。相比之下，Sh通道作用于几十毫秒内的事件，Sh突变会使尖峰变宽并降低放电率，但不会消除任何类型的放电模式。然而，用4-氨基吡啶去除Sh和Shal的I(A)会将延迟放电模式转变为阻尼放电模式，表明它们在调节尖峰起始中的作用。奎尼丁对Shab I(K)的特异性阻断模拟了Shab表型，并将强直放电转变为阻尼模式。这些转变表明不同放电模式背后的钾离子电流相互作用存在复杂程度的层次结构。通过使用GAL4-UAS系统可识别的不同谱系定义的神经元亚群，表现出不同的尖峰特性和钾离子电流组成，为功能特化神经元的突变分析提供了机会。
