The marine secondary metabolites 2,4-dibromophenol and 2,4,6-tribromophenol differentially modulate voltage dependent ion currents in neuroendocrine (PC12) cells

Aquat Toxicol. 2006 Oct 12;79(4):384-90. doi: 10.1016/j.aquatox.2006.07.002. Epub 2006 Jul 11.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Calcium Channels / drug effects*
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Marine Toxins / toxicity*
  • Neurosecretory Systems / cytology
  • Neurosecretory Systems / drug effects*
  • Neurosecretory Systems / physiology
  • Nifedipine / pharmacology
  • PC12 Cells
  • Patch-Clamp Techniques
  • Phenols / toxicity*
  • Rats
  • Time Factors

Substances

  • Calcium Channels
  • Marine Toxins
  • Phenols
  • Nifedipine
  • 2,4-dibromophenol
  • 2,4,6-tribromophenol