Acute functional neurotoxicity of lanthanum(III) in primary cortical networks

Because of its diverse physical and chemical properties, lanthanum has been used in various industrial and medical fields. However, until recently, its effects at the cellular and molecular level had hardly been investigated. Using primary cortical networks grown on microelectrode array neurochips,...

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Published in:Toxicological sciences 2011-03, Vol.120 (1), p.173-183
Main Authors: Gramowski, Alexandra, Jügelt, Konstantin, Schröder, Olaf H-U, Weiss, Dieter G, Mitzner, Steffen
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Action Potentials - physiology
Animals
Cell Culture Techniques
Cells, Cultured
Cerebral Cortex - cytology
Cerebral Cortex - drug effects
Cerebral Cortex - physiology
Data Interpretation, Statistical
Lanthanum - toxicity
Mice
Mice, Inbred Strains
Microarray Analysis
Microelectrodes
Nerve Net - drug effects
Nerve Net - physiology
Neurotoxicity Syndromes - etiology
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Summary:Because of its diverse physical and chemical properties, lanthanum has been used in various industrial and medical fields. However, until recently, its effects at the cellular and molecular level had hardly been investigated. Using primary cortical networks grown on microelectrode array neurochips, we investigated the acute functional neurotoxicity of lanthanum(III) chloride (LaCl(3)). Lanthanum caused a biphasic concentration-dependent decline in network activity resulting in a complete cessation of the activity at 3mM LaCl(3). However, the networks' oscillatory behavior and synchronicity between neurons remained unaffected until activity loss. The spike activity diminished at half effective concentration values for the two phases of 117 nM and 763 μM LaCl(3) corresponding to 16 ng/ml and 10.6 μg/ml lanthanum, respectively. Furthermore, under the experimental conditions, LaCl(3) did not affect voltage-dependent ion channels contributing to the shape and amplitude of the action potential. Further similarity analysis by pattern recognition exposed significant similarities of the activity changes caused by LaCl(3) to those induced by phenobarbital, gamma-aminobutyric acid, and the gap junction blocker carbenoxolone and sodium propionate. Overall, this study demonstrates inhibitory and potentially sedative toxicological effects of lanthanum(III) ions at concentrations comparable to the plasma concentrations observed in patients with kidney disease being treated with lanthanum carbonate for hyperphosphatemia. Therefore, given the lack of proof that the blood-brain barrier is completely impermeable in uremic patients and lanthanum cannot cross, caution is warranted.
ISSN:1096-6080
1096-0929
DOI:10.1093/toxsci/kfq385