On the mechanism of modulation of transient outward current in cultured rat hippocampal neurons by di- and trivalent cations

J Neurophysiol. 1995 Jan;73(1):73-9. doi: 10.1152/jn.1995.73.1.73.


1. The mechanisms of Zn2+ modulation of transient outward current (TOC) were studied in cultured rat hippocampal neurons, using the voltage-clamp technique. In the presence of micromolar concentrations of external Zn2+, the voltage dependence of activation and inactivation was shifted to more positive membrane potentials. The gating of TOC was unaltered by internal application of Zn2+. The effect of Zn2+ were not mimicked by external Ca2+, except at very high concentrations (> 10 mM). 2. The modulatory effects of external Zn2+ on TOC gating were not reproduced, antagonized, nor enhanced by lowering external ionic strength, indicating that modulation by Zn2+ does not occur via screening of bulk surface negative charge. 3. A range of other divalent and trivalent metal ions also was studied, and several were found to modulate the transient outward current when added to the extracellular medium. In particular, Pb2+, La3+, and Gd3+ were potent modulators, showing activity in the low micromolar range. Other metal ions were weaker modulators (e.g., Cd2+) or were without activity at the concentrations tested (Fe3+, Cu2+, Ni2+). 4. The same range of ions also was tested on the delayed rectifier K+ current in cultured rat hippocampal neurons. None of the ions studied had significant effects on delayed rectifier gating, although high (> or = 100 microM) concentrations of Pb2+ and La3+ reduced maximal current amplitude, suggesting the possibility of channel block.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / pharmacology*
  • Cations / pharmacology
  • Cells, Cultured
  • Hippocampus / physiology*
  • Lead / toxicity
  • Membrane Potentials / drug effects
  • Metals
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Potassium Channels
  • Rats
  • Zinc / pharmacology*


  • Cations
  • Metals
  • Potassium Channels
  • Lead
  • Zinc
  • Calcium