Sandow Shaun L, Grayson T Hilton
Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Kensington, Sydney, Australia.
Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H1-7. doi: 10.1152/ajpheart.00042.2009. Epub 2009 May 1.
The potential physiological role of plasmalemmal large-conductance calcium-activated potassium channels (BK(Ca)) in vascular endothelial cells is controversial. Studies of freshly isolated and cultured vascular endothelial cells provide disparate results, both supporting and refuting a role for BK(Ca) in endothelial function. Most studies using freshly isolated, intact, healthy arteries provide little support for a physiological role for BK(Ca) in the endothelium, although recent work suggests that this may not be the case in diseased vessels. In isolated and cultured vascular endothelial cells, the autocrine action of growth factors, hormones, and vasoactive substances results in phenotypic drift. Such an induced heterogeneity is likely a primary factor accounting for the apparent differences, and often enhanced BK(Ca) expression and function, in isolated and cultured vascular endothelial cells. In a similar manner, heterogeneity in endothelial BK(Ca) expression and function in intact arteries may be representative of normal and disease states, BK(Ca) being absent in normal intact artery endothelium and upregulated in disease where dysfunction induces signals that alter channel expression and function. Indeed, in some intact vessels, there is evidence for the presence of BK(Ca), such as mRNA and/or specific BK subunits, an observation that is consistent with the potential for rapid upregulation, as may occur in disease. This perspective proposes that the disparity in the results obtained for BK(Ca) expression and function from freshly isolated and cultured vascular endothelial cells is largely due to variability in experimental conditions and, furthermore, that the expression of BK(Ca) in intact artery endothelium is primarily associated with disease. Although answers to physiologically relevant questions may only be available in atypical physiological conditions, such as those of isolation and culture, the limitations of these methods require open and objective recognition.
质膜大电导钙激活钾通道（BK(Ca)）在血管内皮细胞中的潜在生理作用存在争议。对新鲜分离和培养的血管内皮细胞的研究结果不一，既有支持BK(Ca)在内皮功能中起作用的，也有反驳的。大多数使用新鲜分离的完整健康动脉进行的研究几乎没有为BK(Ca)在内皮中的生理作用提供支持，尽管最近的研究表明在病变血管中情况可能并非如此。在分离和培养的血管内皮细胞中，生长因子、激素和血管活性物质的自分泌作用会导致表型漂移。这种诱导的异质性可能是造成分离和培养的血管内皮细胞中明显差异（通常是BK(Ca)表达和功能增强）的主要因素。同样，完整动脉中内皮BK(Ca)表达和功能的异质性可能代表正常和疾病状态，正常完整动脉内皮中不存在BK(Ca)，而在疾病中功能障碍引发改变通道表达和功能的信号时其表达上调。事实上，在一些完整血管中，有证据表明存在BK(Ca)，如mRNA和/或特定的BK亚基，这一观察结果与疾病中可能发生的快速上调潜力一致。该观点认为，从新鲜分离和培养的血管内皮细胞获得的BK(Ca)表达和功能结果的差异很大程度上是由于实验条件的变异性，此外，完整动脉内皮中BK(Ca)的表达主要与疾病相关。尽管只有在非典型生理条件下，如分离和培养条件下，才能获得与生理相关问题的答案，但这些方法的局限性需要得到公开和客观的认识。
