Wohlrab D, Wohlrab J, Reichel H, Hein W
Department of Orthopaedics, Martin Luther University Halle-Wittenberg, Halle 06097, Germany.
J Orthop Sci. 2001;6(2):155-9. doi: 10.1007/s007760100064.
As in cells in all living cell systems, human chondrocytes are provided with a membrane potential. The existence of ion channels in the cell membrane is an essential prerequisite for the development of membrane potential. In nonhuman chondrocytes, different ion channels have already been identified. An association between potassium channel activity and cell proliferation has been detected in different human cell systems, whereas proof of an association between ion channel activity in human chondrocytes and their proliferation has yet to be established. In this study, we investigated the concentration-dependent influence of the ion channel modulators tetraethylammonium (TEA), 4-aminopyridine (4-AP), 4',4'diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid (SITS), and verapamil (vp) on the membrane potential and the proliferation of human chondrocytes, using flow cytometry. We found that the used ion channel modulators caused a change in the membrane potential of human chondrocytes. The membrane potential was decreased by 18% with 0.25 mmol/l vp (the maximal measurable effect of any of the ion channel modulators) compared with that in a control group. We measured DNA distribution in the human chondrocytes, and it was apparent that they were diploid cells with a very low proliferative tendency. These results allow us to conclude that ion channel modulators influence chondrocyte proliferation. Knowledge of the regulation of chondrocyte proliferation via ion channel modulators could serve in the research of new osteoarthritis treatment concepts.
与所有活细胞系统中的细胞一样，人软骨细胞具有膜电位。细胞膜中离子通道的存在是膜电位形成的必要前提。在非人类软骨细胞中，已经鉴定出了不同的离子通道。在不同的人类细胞系统中已检测到钾通道活性与细胞增殖之间的关联，而人软骨细胞中离子通道活性与其增殖之间的关联证据尚未确立。在本研究中，我们使用流式细胞术研究了离子通道调节剂四乙铵（TEA）、4-氨基吡啶（4-AP）、4',4'-二异硫氰酸根合芪-2,2'-二磺酸（DIDS）、4-乙酰氨基-4'-异硫氰酸根合-2,2'-二磺酸（SITS）和维拉帕米（vp）对人软骨细胞膜电位和增殖的浓度依赖性影响。我们发现所使用的离子通道调节剂导致了人软骨细胞膜电位的变化。与对照组相比，0.25 mmol/l vp（任何一种离子通道调节剂的最大可测量效应）使膜电位降低了18%。我们测量了人软骨细胞中的DNA分布，很明显它们是具有极低增殖倾向的二倍体细胞。这些结果使我们得出结论，离子通道调节剂会影响软骨细胞增殖。通过离子通道调节剂了解软骨细胞增殖的调控，可为新的骨关节炎治疗概念的研究提供帮助。
