Influence of ion channels on the proliferation of human chondrocytes.
The goal of the study was to examine connections between ion channel activity and the proliferation of human chondrocytes. Chondrocytes were isolated form human osteoarthritic knee joint cartilage. In this study 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 stilbene (SITS), verapamil (vp) and lidocaine (lido) on the membrane potential and the proliferation of human chondrocytes was investigated using flow cytometry and the measurement of (3)H-thymidine incorporation as measure for the cell proliferation. The results show an effect of the used ion channel modulators causing a change of the membrane potential of human chondrocytes. The maximal measurable effects of the membrane potential were listed with 0.25 mmol/l verapamil (-18%) and 0.1 mmol/l lidocaine (+20%). When measuring DNA distribution, it became apparent that the human chondrocytes are diploid cells with a very low proliferation tendency. After 12 days culture duration, lidocaine and 4-AP cause an increase of the DNA synthesis rate being a limited effect. These results allow the conclusion of an influence of ion channel modulators on chondrocyte proliferation. To gain knowledge of the regulation of chondrocyte proliferation via ion channel modulators could serve the research of new osteoarthritis treatment concepts.
Wohlrab
David
D
Department of Orthopaedics, Martin Luther University, Halle-Wittenberg, Germany. david.wohlrab@medizin.uni-halle.de
Lebek
Susanne
S
Krüger
Thomas
T
Reichel
Heiko
H
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D018118:Chloride Channels / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015640:Ion Channel Gating; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000473:pathology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018118:Chloride Channels; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D019789:Tetraethylammonium; D008012:Lidocaine; D015761:4-Aminopyridine; D014700:Verapamil; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid