Concentration-dependent modulations of potassium and calcium currents of rat osteoblastic cells by arachidonic acid.
We show that the voltage-gated K+ and Ca2+ currents of rat osteoblastic cells are strongly modulated by arachidonic acid (AA), and that these modulations are very sensitive to the AA concentration. At 2 or 3 microM, AA reduces the amplitude and accelerates the inactivation of the K+ current activated by depolarization; at higher concentrations (> or = 5 microM), AA still blocks this K+ current, but also induces a very large noninactivating K+ current. At 2 or 3 microM, AA enhances the T-type Ca2+ current, close to its threshold of activation, whereas at 10 microM, it blocks that current. AA (1-10 microM) also blocks the dihydropyridine-sensitive L-type Ca2+ current. Thus, the effect of AA on Ca2+ entry through voltage-gated Ca2+ channels can change qualitatively with the AA concentration: at 2 or 3 microM, AA will favor Ca2+ entry through T channels, both by lowering the voltage-gated K+ conductance and by increasing the T current, whereas at 10 microM, AA will prevent Ca2+ entry through voltage-gated Ca2+ channels, both by inducing a K+ conductance and by blocking Ca2+ channels.
Chesnoy-Marchais
D
D
Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris, France.
Fritsch
J
J
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D051381:Rats
D015220:Calcium Channels; D004095:Dihydropyridines; D015221:Potassium Channels; D016718:Arachidonic Acid