On the mechanism of modulation of transient outward current in cultured rat hippocampal neurons by di- and trivalent cations.
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)
Talukder
G
G
Department of Anesthesia and Critical Care, University of Chicago, Illinois 60637.
Harrison
N L
NL
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002412:Cations / Q000494:pharmacology; D002478:Cells, Cultured; D006624:Hippocampus / Q000502:physiology*; D007854:Lead / Q000633:toxicity; D008564:Membrane Potentials / Q000187:drug effects; D008670:Metals; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D051381:Rats; D015032:Zinc / Q000494:pharmacology*
D002412:Cations; D008670:Metals; D015221:Potassium Channels; D007854:Lead; D015032:Zinc; D002118:Calcium