Expression and biophysical properties of Kv1 channels in supragranular neocortical pyramidal neurones

Expression and biophysical properties of Kv1 channels in supragranular neocortical pyramidal neurones
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DOI:
10.1113/jphysiol.2005.097006
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发表时间:
2006-03-01
影响因子:
5.5
通讯作者:
Foehring, RC
Foehring, RC
中科院分区:
医学1区
文献类型:
--
作者:
Guan, D;Lee, JCF;Foehring, RC

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钾通道是神经元兴奋性的多种调节因子。作为神经元如何利用这种分子多样性的研究的一部分,我们检测了来自躯体感觉和运动皮质的第二层/第三层锥体神经元中天然KV1通道的表达和生物物理特性。单细胞RT-PCR、免疫细胞化学和特定多肽毒素的全细胞记录显示,单个锥体细胞表达多个KV1α亚基。亚基含量最高的亚基是Kv1.1、1.2、1.4、1.3。所有这些亚基均定位于躯体树突状细胞和轴突细胞室。这些数据表明这些细胞中KV1通道的亚单位面色的可变性。与α-树突状毒素(α-DTX)不敏感电流相比,α-树突状毒素(α-DTX)敏感电流激活更快,并且在更负的电位下激活,在接近动作电位阈值的电压下首次被观察到,并且对保持电位相对不敏感。在稳态下,α-DTX敏感电流约占外向电流的10%,响应范围为-70 mV。从-50 mV,这一百分比增加到类似的20%。所有细胞均表达α-DTX敏感电流,失活动力学缓慢。在一些细胞中,也存在暂态成分。失活动力学依赖于电压,因此在重复放电过程中,在通过棘波间隔的电位下失活是缓慢的。由于其动力学和电压依赖性,α-DTX敏感电流在生理静息电位和对短暂刺激的反应中应该是最重要的。KV1通道在阈值附近的电压下也应该是重要的,并且对应于棘波间期。
Potassium channels are extremely diverse regulators of neuronal excitability. As part of an investigation into how this molecular diversity is utilized by neurones, we examined the expression and biophysical properties of native Kv1 channels in layer II/III pyramidal neurones from somatosensory and motor cortex. Single-cell RT-PCR, immunocytochemistry, and whole cell recordings with specific peptide toxins revealed that individual pyramidal cells express multiple Kv1 alpha-subunits. The most abundant subunit mRNAs were Kv1.1 > 1.2 > 1.4 > 1.3. All of these subunits were localized to somatodendritic as well as axonal cell compartments. These data suggest variability in the subunit complexion of Kv1 channels in these cells. The alpha-dendrotoxin (alpha-DTX)-sensitive current activated more rapidly and at more negative potentials than the alpha-DTX-insensitive current, was first observed at voltages near action potential threshold, and was relatively insensitive to holding potential. The alpha-DTX-sensitive current comprised about 10% of outward current at steady-state, in response to steps from -70 mV. From -50 mV, this percentage increased to similar to 20%. All cells expressed an alpha-DTX-sensitive current with slow inactivation kinetics. In some cells a transient component was also present. Deactivation kinetics were voltage dependent, such that deactivation was slow at potentials traversed by interspike intervals during repetitive firing. Because of its kinetics and voltage dependence, the alpha-DTX-sensitive current should be most important at physiological resting potentials and in response to brief stimuli. Kv1 channels should also be important at voltages near threshold and corresponding to interspike intervals.