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Effects of lead on cloned voltage-operated neuronal potassium channels

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Abstract

The action of lead (Pb 2+) 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 μmol/l and was maximal at a concentration of about 30 μmol/l. At a potential of − 30 mV, the concentration needed for a 50% reduction of the potassium current was 1.0 μmol/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.

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References

  • Alkondon M, Costa ACS, Radhakrishnan V, Aronstam RS, Albuquerque EX (1990) Selective blockade of NMDA-activated channel currents may be implicated in learning deficits caused by lead. FEBS Lett 261:124–130

    Google Scholar 

  • Audesirk G (1993) Electrophysiology of lead intoxication: Effects on voltage-sensitive ion channels. Neurotoxicology 14:137–148

    Google Scholar 

  • Audesirk G, Audesirk T (1991) Effects of inorganic lead on voltage-sensitive calcium channels in NlE-115 neuroblastoma cells. Neurotoxicology 12:519–528

    Google Scholar 

  • Beckh S, Pongs O (1990) Members of the RCK potassium channel family are differentially expressed in the rat nervous system. EMBO J 9:777–782

    Google Scholar 

  • Binding N, Altrup U, Madeja M, Neidt U, Speckman E-J, Witting U (1994) Neurons of the land snail Helix pomatia in experimental neurotoxicology:influence on extra- and intracellular applied lead on isolated and connected neurons. Zentralbl Hyg Umweltmed 195:222–223

    Google Scholar 

  • Busselberg D, Evans ML, Rahmann H, Carpenter DO (1991a) Lead and zinc block a voltage-activated calcium channel of Aplysia neurons. J Neurophysiol 65:786–795

    Google Scholar 

  • Busselberg D, Evans ML, Rahmann H, Carpenter DO (1991b) Effects of inorganic and triethyl lead and inorganic mercury on the voltage activated calcium channel of Aplysia neurons. Neurotoxicology 12:733–744

    Google Scholar 

  • Cavalleri A, Minoia C, Ceroni M, Poloni M (1984) Lead in cerebrospinal fluid and its relationship to plasma lead in humans. J Appl Toxicol 4:63–65

    Google Scholar 

  • Christie MJ, Adelman JP, Douglass J, North RA (1989) Expression of a cloned rat brain potassium channel in Xenopus oocytes. Science 244:221–224

    Google Scholar 

  • Dascal N (1987) The use of Xenopus oocytes for the study of ion channels. Crit Rev Biochem Mol Biol 22:317–387

    Google Scholar 

  • Dumont JN (1972) Oogenesis in Xenopus laevis (Daudin) I. Stages of ooocyte development in laboratory maintained animals. J Morphol 136:153–180

    Google Scholar 

  • Evans ML, Busselberg D, Carpenter DO (1991) Pb2+ blocks calcium currents of cultured dorsal root ganglion cells. Neurosci Lett 129:103–106

    Google Scholar 

  • Grandjean P (1978) Regional distribution of lead in human brains. Toxicol Lett 2:65–69

    Google Scholar 

  • Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391:85–100

    CAS  PubMed  Google Scholar 

  • Hille B (1992) Ionic Channels of Excitable Membranes 2nd edn. Sinauer Associates, Sunderland.

    Google Scholar 

  • Hille B, Woodhulll AM, Shapiro BI (1975) Negative surface charge near sodium channels of nerve: Divalent ions, monovalent ions, and pH. Philos Trans R Soc Lond [Biol] 270:301–318

    Google Scholar 

  • Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529–531

    Google Scholar 

  • Kostyuk PG, Mironov SL, Doroshenko PA, Ponomarev VN (1982) Surface charges on the outer side of the mollusc neuron membrane. J Membr Biol 70:171–179

    Google Scholar 

  • Kues WA, Wunder F (1992) Heterogeneous expression patterns of mammalian potassium channel genes in developing and adult rat brain. Eur J Neurosci 4:1296–1308

    Google Scholar 

  • Lu L, Montrose-Rafizadeh C, Hwang T-C, Gugginio WB (1990) A delayed rectifier potassium current in Xenopus oocytes. Biophys J 57:1117–1123

    Google Scholar 

  • Madeja M, Mußhoff U, Speckmann E-J (1991) A concentration-clamp system allowing two-electrode voltage-clamp investigations in oocytes of Xenopus laevis. J Neurosci Methods 38:267–269

    Google Scholar 

  • Methfessel C, Witzemann V, Takahashi T, Mishina M, Numa S, Sakmann B (1986) Patch clamp mesurements on Xenopus laevis oocytes:currents through endogenous channels and implanted acetylcholine receptor and sodium channels. Pflugers Arch 407:577–588

    Google Scholar 

  • Nathanson JA, Bloom FE (1976) Heavy metals and adenosine cyclic 3′,5′-monophosphate metabolism: possible relevance to heavy metal toxicity. Mol Pharmacol 12:390–398

    Google Scholar 

  • Pongs O (1992) Molecular biology of voltage-dependent potassium channels. Physiol Rev 72:S69-S88

    Google Scholar 

  • Reuveny E, Narahashi T (1991) Potent blocking action of lead on voltage-activated calcium channels in human neuroblstoma cells SH-SY5Y. Brain Res 545:312–314

    Google Scholar 

  • Simons TJB (1993) Lead transport and binding by human erythrocytes in vitro. Pflügers Arch 423:307–313

    Google Scholar 

  • Stühmer W, Stocker M, Sakmann B, Seeburg P, Baumann A, Grupe A, Pongs O (1988) potassium channels expressed from rat brain cDNA have delayed rectifier properties. FEBS Lett 242: 199–206

    Google Scholar 

  • Stühmer W, Ruppersberg JP, Schröter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, Pongs O (1989) Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J 8:3235–3244

    Google Scholar 

  • Uteshev V, Büsselberg D, Haas HL (1993) Pb2+ modulates the NMDA-receptor-channel complex. Naunyn Schmiedebergs Arch Pharmacol 347:209–213

    Google Scholar 

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Madeja, M., Binding, N., Mußhoff, U. et al. Effects of lead on cloned voltage-operated neuronal potassium channels. Naunyn-Schmiedeberg's Arch Pharmacol 351, 320–327 (1995). https://doi.org/10.1007/BF00233254

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