title: Acute functional neurotoxicity of lanthanum(III) in primary cortical networks.
abstract: 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.
authors.affiliation: University of Rostock, Institute for Biological Sciences, Cell Biology, and Biosystems Technology, 18059 Rostock, Germany. alexandra.gramowski@uni-rostock.de
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gramowski
authors.forename: Konstantin
authors.initials: K
authors.lastname: Jügelt
authors.forename: Olaf H-U
authors.initials: OH
authors.lastname: Schröder
authors.forename: Dieter G
authors.initials: DG
authors.lastname: Weiss
authors.forename: Steffen
authors.initials: S
authors.lastname: Mitzner
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D003627:Data Interpretation, Statistical; D007811:Lanthanum / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D046228:Microarray Analysis; D008839:Microelectrodes; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology; D020258:Neurotoxicity Syndromes / Q000209:etiology*
chemical_list: C028521:lanthanum chloride; D007811:Lanthanum