Effects of lead on cloned voltage-operated neuronal potassium channels.
The action of lead (Pb2+) on cloned voltage-operated potassium channels of the rat brain was investigated in oocytes of Xenopus laevis. Pb2+ was found to decrease the potassium currents. This effect was due to a shift of the current-voltage relation in a positive direction (up to 30 mV). The Pb2+ effect appeared at a threshold concentration of about 0.1 mumol/l and was maximal at a concentration of about 30 mumol/l. At a potential of -30 mV, the concentration needed for a 50% reduction of the potassium current was 1.0 mumol/l. The depressant effect of Pb2+ was obtained with all potassium channels tested (Kv1.1, Kv1.2, Kv1.4, Kv2.1, Kv3.4). It was minimal for the Kv2.1 channel and maximal for the Kv1.1 channel at potentials negative to 0 mV. An effect comparable with that of Pb2+ could not be induced by the application of magnesium or calcium. The external application of Pb2+ led to a decrease of potassium currents in outside-out but not in inside-out membrane patches. Overall, Pb2+ had a significant effect on the potassium channels which may contribute to the mechanisms of Pb2+ neurotoxicity.
Madeja
M
M
Institut für Physiologie, Münster, Germany.
Binding
N
N
Musshoff
U
U
Pongs
O
O
Witting
U
U
Speckmann
E J
EJ
D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D003001:Cloning, Molecular; D004594:Electrophysiology; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D014982:Xenopus laevis
D002413:Cations, Divalent; D015221:Potassium Channels; D007854:Lead; D012313:RNA