Flow-activated Chloride Channels in Vascular Endothelium
Flow-activated Chloride Channels in Vascular Endothelium
复制标题
血管内皮中的流激活氯离子通道
DOI：
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发表时间：
2006
影响因子：
4.8
通讯作者：
A. Barakat
中科院分区：
文献类型：
--
作者：
M. Gautam;Yue;T. Thirkill;G. Douglas;A. Barakat
虽然外向整流氯离子通道的激活是内皮细胞（EC）对切应力最快的反应之一，但对这些通道的了解甚少。在这项研究中，我们使用全细胞膜片钳记录来表征牛主动脉内皮细胞（BAECs）的流动激活的Cl-电流。剪切应力的应用诱导了Cl-电流的快速发展，该电流可被Cl-通道拮抗剂5-硝基-2-（3-苯丙氨基）苯甲酸（100 μm）有效阻断。电流在低至0.3达因/cm 2的剪切应力下开始，在流动开始的几分钟内达到其峰值，并且在3.5达因/cm 2以上饱和（比流动前水平增加约2.5-3.5倍）。Cl-电流脱敏缓慢响应于持续的流量，和步骤的剪切应力的增加引起增加的电流，只有当剪切应力水平低于3.5达因/cm 2的饱和水平。生理振荡频率为1 Hz的振荡流，如发生在易发生动脉粥样硬化的扰动流区，未能引起Cl-电流，而较低的振荡频率导致电流的部分恢复。通常认为对动脉粥样硬化有保护作用的非反向脉动流在引发电流方面与稳定流一样有效。使用不同粘度的流体的测量表明，Cl-电流是响应于剪切应力，而不是剪切速率。阻断血流激活的Cl-通道可抑制BAEC中的Akt磷酸化，而阻断血流敏感的K+通道则无影响，提示血流激活的Cl-通道在调节EC血流信号中起重要作用。
Although activation of outward rectifying Cl– channels is one of the fastest responses of endothelial cells (ECs) to shear stress, little is known about these channels. In this study, we used whole-cell patch clamp recordings to characterize the flow-activated Cl– current in bovine aortic ECs (BAECs). Application of shear stress induced rapid development of a Cl– current that was effectively blocked by the Cl– channel antagonist 5-nitro-2-(3-phenopropylamino)benzoic acid (100 μm). The current initiated at a shear stress as low as 0.3 dyne/cm2, attained its peak within minutes of flow onset, and saturated above 3.5 dynes/cm2 (∼2.5–3.5-fold increase over pre-flow levels). The Cl– current desensitized slowly in response to sustained flow, and step increases in shear stress elicited increased current only if the shear stress levels were below the 3.5 dynes/cm2 saturation level. Oscillatory flow with a physiological oscillation frequency of 1 Hz, as occurs in disturbed flow zones prone to atherosclerosis, failed to elicit the Cl– current, whereas lower oscillation frequencies led to partial recovery of the current. Nonreversing pulsatile flow, generally considered protective of atherosclerosis, was as effective in eliciting the current as steady flow. Measurements using fluids of different viscosities indicated that the Cl– current is responsive to shear stress rather than shear rate. Blocking the flow-activated Cl– current abolished flow-induced Akt phosphorylation in BAECs, whereas blocking flow-sensitive K+ currents had no effect, suggesting that flow-activated Cl– channels play an important role in regulating EC flow signaling.
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影响因子：
20.1
作者：
Barakat, AI;Leaver, EV;Davies, PF
通讯作者：
Davies, PF
DOI：
10.1115/1.2891384
发表时间：
1992-08-01
影响因子：
1.7
作者：
NEREM, RM
通讯作者：
NEREM, RM
DOI：
10.1073/pnas.94.8.3726
发表时间：
1997-04
影响因子：
11.1
作者：
Theodore F. Wiesner;B. C. Berk;Androbertm . Nerem
通讯作者：
Theodore F. Wiesner;B. C. Berk;Androbertm . Nerem
流体剪切应力对牛主动脉内皮细胞体积调节阴离子电流的双重影响。
DOI：
10.1152/ajpcell.00247.2001
发表时间：
2002
期刊：
American journal of physiology. Cell physiology
影响因子：
--
作者：
Romanenko,VictorG;Davies,PeterF;Levitan,Irena
通讯作者：
Levitan,Irena