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新生大鼠大脑皮层锥体神经元 A 型钾电流和 Kv1- 和 Kv2- 介导钾电流的发育。

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons.

机构信息

Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

出版信息

J Neurophysiol. 2011 Jun;105(6):2976-88. doi: 10.1152/jn.00758.2010. Epub 2011 Mar 30.

Abstract

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K(+) channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K(+) currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex. Both the persistent/slowly inactivating and transient components of the total K(+) current increased in density with postnatal age. We used specific pharmacological agents to test the relative contributions of putative Kv1- and Kv2-mediated currents (100 nM α-dendrotoxin and 600 nM stromatoxin, respectively). A combination of voltage protocol, pharmacology, and curve fitting was used to isolate the rapidly inactivating A-type current. We found that the density of all identified current components increased with postnatal age, approaching a plateau at 3-5 wk. We found no significant changes in the relative proportions or kinetics of any component between postnatal weeks 1 and 5, except that the activation time constant for A-type current was longer at 1 wk. The putative Kv2-mediated component was the largest at all ages. Immunocytochemistry indicated that protein expression for Kv4.2, Kv4.3, Kv1.4, and Kv2.1 increased between 1 wk and 4-5 wk of age.

摘要

钾通道调节神经元兴奋性的众多方面,并且已经在大鼠新皮层的锥体神经元中鉴定出几种电压门控 K(+) 通道亚基。以前的研究要么将外向电流的发展视为一个整体,要么将电流分为瞬时、A 型和持久、延迟整流成分,但没有区分由 α-亚基类型定义的电流成分。为了便于比较报告来自不同年龄动物的 K(+) 电流的研究,并了解特定电流成分的功能作用,我们在大鼠体感皮层 II/III 层的锥体神经元中表征了鉴定出的 Kv 通道介导的电流的出生后发育。总 K(+) 电流的持久/缓慢失活和瞬态成分的密度都随出生后年龄而增加。我们使用特定的药理学试剂来测试假定的 Kv1 和 Kv2 介导的电流的相对贡献(分别为 100 nM α-树突毒素和 600 nM stromatoxin)。我们使用电压方案、药理学和曲线拟合的组合来分离快速失活的 A 型电流。我们发现所有鉴定出的电流成分的密度都随出生后年龄的增加而增加,在 3-5 周时达到平台。我们发现除了 A 型电流的激活时间常数在 1 周时更长外,在 1 至 5 周龄之间,任何成分的相对比例或动力学都没有明显变化。假定的 Kv2 介导的成分在所有年龄段都是最大的。免疫细胞化学表明 Kv4.2、Kv4.3、Kv1.4 和 Kv2.1 的蛋白表达在 1 周至 4-5 周龄之间增加。

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