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Kv1.3电压门控钾离子通道亚基在大鼠前列腺癌细胞系中的主要表达:电生理学、药理学及分子特征分析

Predominant expression of Kv1.3 voltage-gated K+ channel subunit in rat prostate cancer cell lines: electrophysiological, pharmacological and molecular characterisation.

作者信息

Fraser S P, Grimes J A, Diss J K J, Stewart D, Dolly J O, Djamgoz M B A

机构信息

Department of Biological Sciences, Imperial College of Science, Technology and Medicine, Sir Alexander Fleming Building, London SW7 2AZ, UK.

出版信息

Pflugers Arch. 2003 Aug;446(5):559-71. doi: 10.1007/s00424-003-1077-0. Epub 2003 Jul 1.

Abstract

Voltage-gated K+ currents expressed in two rat prostate cancer ("Dunning") cell lines of markedly different metastatic ability were characterised using electrophysiological, pharmacological and molecular approaches. Whole-cell patch-clamp recordings showed that both strongly metastatic MAT-LyLu and weakly metastatic AT-2 cell lines possessed outward (delayed-rectifier type) K+ currents, which activated at around -40 mV. From the parameters measured, several characteristics of the two cell lines were similar. However, a number of statistically significant differences were noted for MAT-LyLu versus the AT-2 cells as follows: (1) current densities were smaller; (2) the slope factor for channel activation was smaller; (3) the voltage at which current was half-inactivated, and the slope factor for channel inactivation were greater; (4) the time constants for current decay at -20 and 0 mV were smaller; and (5) the residual peak current was larger following 60 s of repetitive voltage pulses for stimulation frequencies in the range 0.05-0.2 Hz. On the other hand, the K+ currents in both cell lines showed similar pharmacological profiles. Thus, the currents were blocked by 4-aminopyridine, tetraethylammonium, verapamil, margatoxin, and charybdotoxin, with highly similar IC(50)s for given blockers. The electrophysiological and pharmacological data taken together suggested expression of voltage-gated K+ channels of the Kv1 family, expression of the Kv1.3 subunit being predominant. Western blot and RT-PCR tests both confirmed that the cells indeed expressed Kv1.3 and to a lesser extent Kv1.4 and Kv1.6 channel alpha-subunits. In view of the similarity of channel expression in the two cell lines, voltage-gated K+ channel activity may not be a primary determinant of metastatic potential in the rat model of prostate cancer, but the possible contribution of K+ channel activity to the metastatic process is discussed.

摘要

采用电生理学、药理学和分子生物学方法,对两种具有明显不同转移能力的大鼠前列腺癌(“邓宁”)细胞系中表达的电压门控钾离子电流进行了表征。全细胞膜片钳记录显示,高转移性的MAT-LyLu细胞系和低转移性的AT-2细胞系均具有外向(延迟整流型)钾离子电流,该电流在约-40 mV时激活。根据测量参数,两种细胞系的一些特征相似。然而,MAT-LyLu细胞与AT-2细胞相比存在一些统计学上的显著差异,如下所示:(1)电流密度较小;(2)通道激活的斜率因子较小;(3)电流半失活时的电压以及通道失活的斜率因子较大;(4)在-20 mV和0 mV时电流衰减的时间常数较小;(5)对于0.05 - 0.2 Hz范围内的刺激频率,在重复电压脉冲60秒后,残余峰值电流较大。另一方面,两种细胞系中的钾离子电流显示出相似的药理学特征。因此,这些电流被4-氨基吡啶、四乙铵、维拉帕米、玛格毒素和蝎毒素阻断,对于给定的阻断剂,其IC(50)高度相似。综合电生理学和药理学数据表明,存在Kv1家族的电压门控钾离子通道表达,其中Kv1.3亚基的表达占主导。蛋白质免疫印迹和逆转录-聚合酶链反应测试均证实,这些细胞确实表达Kv1.3,以及在较小程度上表达Kv1.4和Kv1.6通道α亚基。鉴于两种细胞系中通道表达的相似性,电压门控钾离子通道活性可能不是大鼠前列腺癌模型中转移潜能的主要决定因素,但本文讨论了钾离子通道活性对转移过程的可能贡献。

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