Metal Interactions with Voltage- and Receptor-Activated Ion Channels

Effects of Pb and several other metal ions on various distinct types of voltage-, receptor- and Ca-activated ion channels have been investigated in cultured N1E-115 mouse neuroblastoma cells. Experiments were performed using the whole-cell voltage clamp and single-channel patch clamp techniques. Ext...

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Bibliographic Details
Published in:Environmental health perspectives 1994-09, Vol.102 (suppl 3), p.153-158
Main Authors: Henk P. M. Vijverberg, Oortgiesen, Marga, Leinders, Trese, Regina G. D. M. van Kleef
Format: Article
Language:English
Subjects:
Animals
Cholinergic receptors
Cultured cells
Ion Channel Gating - physiology
Ion channels
Ion Channels - metabolism
Ion currents
Large conductance calcium activated potassium channels
Metal ions
Metals - metabolism
Mice
Neuroblastoma
Neurons
Neurons - metabolism
Patch-Clamp Techniques
Receptors
Receptors, Nicotinic - metabolism
Receptors, Serotonin - metabolism
Serotonin receptors
Toxicity: Molecular and Cellular Mechanisms
Tumor Cells, Cultured
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Summary:Effects of Pb and several other metal ions on various distinct types of voltage-, receptor- and Ca-activated ion channels have been investigated in cultured N1E-115 mouse neuroblastoma cells. Experiments were performed using the whole-cell voltage clamp and single-channel patch clamp techniques. External superfusion of nanomolar to submillimolar concentrations of Pb causes multiple effects on ion channels. Barium current through voltage-activated Ca channels is blocked by micromolar concentrations of Pb, whereas voltage-activated Na current appears insensitive. Neuronal type nicotinic acetylcholine receptor-activated ion current is blocked by nanomolar concentrations of Pb and this block is reversed at micromolar concentrations. Serotonin 5- HT3receptor-activated ion current is much less sensitive to Pb. In addition, external superfusion with micromolar concentrations of Pb as well as of Cd and aluminum induces inward current, associated with the direct activation of nonselective cation channels by these metal ions. In excised inside-out membrane patches of neuroblastoma cells, micromolar concentrations of Ca activate small (SK) and big (BK) Ca-activated K channels. Internally applied Pb activates SK and BK channels more potently than Ca, whereas Cd is approximately equipotent to Pb with respect to SK channel activation, but fails to activate BK channels. The results show that metal ions cause distinct, selective effects on the various types of ion channels and that metal ion interaction sites of ion channels may be highly selective for particular metal ions.
ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.94102s3153