Is the proliferation of human chondrocytes regulated by ionic channels?

Abstract

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.