Wang Ya-Jean, Sung Ruey J, Lin Ming-Wei, Wu Sheng-Nan
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, No. 1, University Road, Tainan, 701, Taiwan.
J Membr Biol. 2006;213(3):175-85. doi: 10.1007/s00232-007-0027-8. Epub 2007 May 4.
Cardiac fibroblasts are involved in the maintenance of myocardial tissue structure. However, little is known about ion currents in human cardiac fibroblasts. It has been recently reported that cardiac fibroblasts can interact electrically with cardiomyocytes through gap junctions. Ca(2+)-activated K(+) currents (I (K[Ca])) of cultured human cardiac fibroblasts were characterized in this study. In whole-cell configuration, depolarizing pulses evoked I (K(Ca)) in an outward rectification in these cells, the amplitude of which was suppressed by paxilline (1 microM: ) or iberiotoxin (200 nM: ). A large-conductance, Ca(2+)-activated K(+) (BK(Ca)) channel with single-channel conductance of 162 +/- 8 pS was also observed in human cardiac fibroblasts. Western blot analysis revealed the presence of alpha-subunit of BK(Ca) channels. The dynamic Luo-Rudy model was applied to predict cell behavior during direct electrical coupling of cardiomyocytes and cardiac fibroblasts. In the simulation, electrically coupled cardiac fibroblasts also exhibited action potential; however, they were electrically inert with no gap-junctional coupling. The simulation predicts that changes in gap junction coupling conductance can influence the configuration of cardiac action potential and cardiomyocyte excitability. I (k(Ca)) can be elicited by simulated action potential waveforms of cardiac fibroblasts when they are electrically coupled to cardiomyocytes. This study demonstrates that a BK(Ca) channel is functionally expressed in human cardiac fibroblasts. The activity of these BK(Ca) channels present in human cardiac fibroblasts may contribute to the functional activities of heart cells through transfer of electrical signals between these two cell types.
心脏成纤维细胞参与心肌组织结构的维持。然而，关于人类心脏成纤维细胞中的离子电流却知之甚少。最近有报道称，心脏成纤维细胞可通过缝隙连接与心肌细胞进行电相互作用。本研究对培养的人类心脏成纤维细胞的钙激活钾电流（I（K[Ca]））进行了表征。在全细胞模式下，去极化脉冲在这些细胞中诱发外向整流的I（K（Ca）），其幅度被帕吉林（1微摩尔：）或iberiotoxin（200纳摩尔：）抑制。在人类心脏成纤维细胞中还观察到一种单通道电导为162±8皮秒的大电导钙激活钾（BK（Ca））通道。蛋白质印迹分析显示存在BK（Ca）通道的α亚基。应用动态Luo-Rudy模型预测心肌细胞和心脏成纤维细胞直接电耦合期间的细胞行为。在模拟中，电耦合的心脏成纤维细胞也表现出动作电位；然而，在没有缝隙连接耦合时它们是电惰性的。模拟预测缝隙连接耦合电导的变化可影响心脏动作电位的形态和心肌细胞兴奋性。当心脏成纤维细胞与心肌细胞电耦合时，模拟动作电位波形可诱发I（k（Ca））。本研究表明BK（Ca）通道在人类心脏成纤维细胞中功能性表达。人类心脏成纤维细胞中存在的这些BK（Ca）通道的活性可能通过这两种细胞类型之间的电信号传递对心脏细胞的功能活动有贡献。
