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J Neurophysiol 78: 2649-2654, 1997;
0022-3077/97 $5.00
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The Journal of Neurophysiology Vol. 78 No. 5 November 1997, pp. 2649-2654
Copyright ©1997 The American Physiological Society

Effects of Pb2+ on Delayed-Rectifier Potassium Channels in Acutely Isolated Hippocampal Neurons

Michael Madeja1, Ulrich Mubeta hoff1, Norbert Binding2, Ute Witting2, and Erwin-Josef Speckmann1

1 Institut für Physiologie and 2 Institut für Arbeitsmedizin, D-48149 Muenster, Germany

Madeja, Michael, Ulrich Mubeta hoff, Norbert Binding, Ute Witting, and Erwin-Josef Speckmann. Effects of Pb2+ on delayed-rectifier potassium channels in acutely isolated hippocampal neurons. J. Neurophysiol. 78: 2649-2654, 1997. The effects of Pb2+ on delayed-rectifier potassium currents were studied in acutely isolated hippocampal neurons (CA1 neurons, CA3 neurons, granule cells) from the guinea pig using the patch-clamp technique in the whole cell configuration. Pb2+ in micromolar concentrations decreased the potassium currents in a voltage-dependent manner, which appeared as a shift of the current-voltage relation to positive potentials. The effect was reversible after washing. The concentration-responsiveness measured in CA1 neurons revealed an IC50 value of 30 µmol/l at a potential of -30 mV. The half-maximal shift of the current-voltage relation was reached at 33 µmol/l and the maximal obtainable shift was 13.4 mV. For the different types of hippocampal neurons, the shift of the current-voltage relation was distinct and was 7.9 mV in CA1 neurons, 13.7 mV in CA3 neurons, and 14.2 mV in granule cells with 50 µmol/l Pb2+. The effects described here of Pb2+ on the potassium currents in hippocampal neurons and the differences between the types of hippocampal neurons correspond with the known properties and distributions of cloned potassium channels found in the hippocampus. As a whole, our results demonstrate that Pb2+ in micromolar concentration is a voltage-dependent, reversible blocker of delayed-rectifier potassium currents of hippocampal neurons. This effect has to be taken into consideration as a possible contributing mechanism for the neurological symptoms of enhanced brain activity seen during Pb2+ intoxication.






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