K+ currents in human coronary artery vascular smooth muscle cells
K+ currents in human coronary artery vascular smooth muscle cells
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DOI：
10.1161/01.res.78.4.676
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发表时间：
1996-04-01
影响因子：
20.1
通讯作者：
Haller, H
中科院分区：
文献类型：
--
作者：
Gollasch, M;Ried, C;Haller, H
K+通道及其电流对于血管张力调节很重要，并且是潜在的治疗靶点；然而，人冠状动脉血管平滑肌细胞（VSMC）中的 K+ 通道却很少受到关注。我们使用制霉菌素的传统膜片钳或穿孔贴片技术检查了从人冠状动脉（n = 368，来自 32 个人心脏）新鲜分离的 VSMC 中的 K+ 电流。我们检测到四种不同的 K+ 电流： (1) 延迟整流器 K+ 电流，I-K(dr)； (2) Ca2+激活的K-电流，I-K(Ca)； (3) 非整流非失活向外 ATP 依赖性 K+ 电流，I-K(ATP)； (4) 自发瞬态向外 K+ 电流 I-K(STOC)。自发瞬时外向电流背后的 K+ 通道可能代表 Ca2+ 激活的 K+ 通道的单个簇群，其功能与肌浆网中的 Ca2+ 释放通道相关。没有观察到内向整流K+电流。 K+电流分布不均匀，因为并非所有细胞都均匀地表现出它们。最突出的 K+ 电流是 I-K(Ca) (100%) 和 I-K(dr) (46%)。 I-K(STOC) 存在于 67% 的 VSMC 中，此前尚未在人类中描述过。生理条件下I-K(ATP)较小；然而，用外源性或内源性冠状血管扩张剂刺激细胞后，I-K(ATP) 显着增加。因此，I-K(ATP) 可能与缺血特别相关，并且作为治疗靶点可能具有特别重要的意义。我们得出的结论是，人类冠状动脉血管平滑肌细胞具有独特的 K+ 电流，与其他物种的电流有很大不同，因此对人类材料的研究具有临床相关性。这些发现为进一步治疗研究提供了潜在途径。
K+ channels and their currents are important in vascular tone regulation and are potential therapeutic targets; however, K+ channels in human coronary artery vascular smooth muscle cells (VSMCs) have received little attention. We examined K+ currents in freshly isolated VSMCs from human coronary arteries (n=368 from 32 human hearts) with conventional patch-clamp or perforated-patch techniques with nystatin. We detected four different K+ currents: (1) the delayed rectifier K+ current, I-K(dr); (2) the Ca2+-activated K- current, I-K(Ca); (3) the nonrectifying noninactivating outward ATP-dependent K+ current, I-K(ATP); and (4) the spontaneous transient outward K+ current, I-K(STOC). K+ channels underlying spontaneous transient outward currents probably represent a single clustered population of Ca2+-activated K+ channels functionally associated with Ca2+ release channels in the sarcoplasmic reticulum. Inwardly rectifying K+ currents were not observed. K+ currents were unevenly distributed in that they were not uniformly exhibited by all cells. The most prominent K+ currents were I-K(Ca) (100%) and I-K(dr) (46%). I-K(STOC)s, which have not been previously described in humans, were present in 67% of VSMCs. I-K(ATP) was small under physiological conditions; however, I-K(ATP) increased markedly after cell stimulation with exogenous or endogenous coronary vasodilators. Thus, I-K(ATP) may be particularly relevant in ischemia and could be of special importance as a therapeutic target. We conclude that human coronary VSMCs have unique K+ currents that differ sufficiently from those of other species, thus making the investigation of human material clinically relevant. The findings suggest potential avenues for further therapeutic research.