The marine secondary metabolites 2,4-dibromophenol and 2,4,6-tribromophenol differentially modulate voltage dependent ion currents in neuroendocrine (PC12) cells.
2,4-Dibromophenol (2,4-DBP) and 2,4,6-tribromophenol (2,4,6-TBP) are marine secondary metabolites, with 2,4,6-tribromophenol playing an important role as industrially produced flame retardant and pesticide. Both substances disturb cellular calcium signals in neuroendocrine cells as previously shown by Hassenklöver et al. (2006) [Hassenklöver, T., Predehl, S., Pilli, J., Ledwolorz, J., Assmann, M., Bickmeyer, U., 2006. Bromophenols, both present in marine organisms and in industrial flame retardants, disturb cellular Ca(2+) signaling in neuroendocrine cells (PC12). Aquat. Toxicol. 76, 37-45]. We investigated calcium channel currents in detail and outward membrane currents as potential cellular targets of both bromophenols. In this electrophysiological approach, 2,4-DBP reduced voltage dependent calcium channel currents with a half-maximal concentration of 45+/-32 microM (S.D.) and a Hill coefficient of 0.87+/-0.49 (S.D.). 2,4,6-TBP reduced calcium channel currents with a half-maximal concentration of 28+/-19 microM (S.D.) and a Hill coefficient of 0.79+/-0.31 (S.D.). The major contribution to calcium channel currents was mediated by L-type (67%) and N-type channels (30%) in PC12 cells; both bromophenols modulated both current types. Whole cell outward currents, mainly carried by potassium ions, were reduced by 2,4-DBP with a half-maximal concentration of 41+/-9 microM (S.D.) showing a Hill coefficient of 1.71+/-0.31 (S.D.). 2,4,6-TBP showed a weak reduction of outward currents at high concentrations of 300 microM. 2,4,6-TBP selectively decreased calcium entry via calcium channels as revealed in whole cell patch clamp experiments, whereas 2,4-DBP reduced both in- and outward currents.
Hassenklöver
Thomas
T
Biologische Anstalt Helgoland, Alfred Wegener Institut für Polar- und Meeresforschung in der Helmholtz Gemeinschaft, Kurpromenade 201, 27483 Helgoland, Germany.
Bickmeyer
Ulf
U
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008387:Marine Toxins / Q000633:toxicity*; D009490:Neurosecretory Systems / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
D015220:Calcium Channels; D008387:Marine Toxins; D010636:Phenols; D009543:Nifedipine; C013930:2,4-dibromophenol; C004554:2,4,6-tribromophenol