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

Toxicol Sci. 2011 Mar;120(1):173-83. doi: 10.1093/toxsci/kfq385. Epub 2010 Dec 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • lanthanum chloride
  • Lanthanum