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大鼠内侧前额叶皮质锥体神经元中类TREK-2通道的活性取决于细胞质钙。

Activity of TREK-2-like Channels in the Pyramidal Neurons of Rat Medial Prefrontal Cortex Depends on Cytoplasmic Calcium.

作者信息

Dworakowska Beata, Gawlak Maciej, Nurowska Ewa

机构信息

Department of Physics and Biophysics, Institute of Biology, Warsaw University of Life Sciences, 02-776 Warsaw, Poland.

Laboratory of Physiology and Pathophysiology, Centre for Preclinical Research and Technology, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland.

出版信息

Biology (Basel). 2021 Oct 30;10(11):1119. doi: 10.3390/biology10111119.

DOI:10.3390/biology10111119
PMID:34827112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8614805/
Abstract

TREK-2-like channels in the pyramidal neurons of rat prefrontal cortex are characterized by a wide range of spontaneous activity-from very low to very high-independent of the membrane potential and the stimuli that are known to activate TREK-2 channels, such as temperature or membrane stretching. The aim of this study was to discover what factors are involved in high levels of TREK-2-like channel activity in these cells. Our research focused on the PI(4,5)P2-dependent mechanism of channel activity. Single-channel patch clamp recordings were performed on freshly dissociated pyramidal neurons of rat prefrontal cortexes in both the cell-attached and inside-out configurations. To evaluate the role of endogenous stimulants, the activity of the channels was recorded in the presence of a PI(4,5)P2 analogue (PI(4,5)P2DiC8) and Ca. Our research revealed that calcium ions are an important factor affecting TREK-2-like channel activity and kinetics. The observation that calcium participates in the activation of TREK-2-like channels is a new finding. We showed that PI(4,5)P2-dependent TREK-2 activity occurs when the conditions for PI(4,5)P2/Ca nanocluster formation are met. We present a possible model explaining the mechanism of calcium action.

摘要

大鼠前额叶皮层锥体神经元中的类TREK-2通道具有广泛的自发活动特性——从极低到极高——且与膜电位以及已知能激活TREK-2通道的刺激因素（如温度或膜拉伸）无关。本研究的目的是探究这些细胞中高水平类TREK-2通道活性涉及哪些因素。我们的研究聚焦于通道活性的磷脂酰肌醇-4,5-二磷酸（PI(4,5)P2）依赖性机制。采用细胞贴附式和内面向外式记录模式，对新鲜解离的大鼠前额叶皮层锥体神经元进行单通道膜片钳记录。为评估内源性刺激物的作用，在存在PI(4,5)P2类似物（PI(4,5)P2DiC8）和钙离子的情况下记录通道活性。我们的研究表明，钙离子是影响类TREK-2通道活性和动力学的重要因素。钙离子参与类TREK-2通道激活这一观察结果是一项新发现。我们发现，当满足PI(4,5)P2/钙离子纳米簇形成的条件时，PI(4,5)P2依赖性的TREK-2活性就会出现。我们提出了一个可能解释钙离子作用机制的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fcb/8614805/f2be8e0a9066/biology-10-01119-g012.jpg
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Genetic and pharmacological inhibition of two-pore domain potassium channel TREK-1 alters depression-related behaviors and neuronal plasticity in the hippocampus in mice.基因和药理学抑制双孔域钾通道 TREK-1 改变了小鼠海马中与抑郁相关的行为和神经元可塑性。
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