Evaluation of Zinc Toxicity Using Neuronal Networks on Microelectrode Arrays: Response Quantification and Entry Pathway Analysis

Murine neuronal networks, derived from embryonic frontal cortex (FC) tissue grown on microelectrode arrays, were used to investigate zinc toxicity at concentrations ranging from 20 to 2000 mM total zinc acetate added to the culture medium. Continual multi-channel recording of spontaneous action potential generation allowed a quantitative analysis of the temporal evolution of network spike activity generation at specific zinc acetate concentrations. Cultures responded with immediate concentration-dependent excitation lasting from 5 to 50 min, consisting of increased spiking and enhanced, coordinated bursting. This was followed by irreversible activity decay. The time to 50% and 90% activity loss was concentration dependent, highly reproducible, and formed linear functions in log-log plots. Network activity loss generally preceded morphological changes. 20% cell swelling was correlated with 50% activity loss. Cultures pretreated with the GABAA receptor antagonists bicuculline (40 mM) and picrotoxin (1 mM) lacked the initial excitation phase. This suggests that zinc-induced excitation may be mediated by interfering with GABA inhibition. Partial network protection was achieved by stopping spontaneous activity with either tetrodotoxin (200 nM) or lidocaine (250 mM). However, recovery was not complete and slow deterioration of network activity continued over 6 hrs. Removal of zinc by early medium changes showed irreversible, catastrophic network failure to develop in a concentration-dependent time window between 50% and 90% activity loss. Investigation of entry routes suggested the L-type but not N-type calcium channels to be the main entry pathway for zinc. Data are presented implicating the chloride channel to be an additional entry route.

Grantor dc:publisher

University of North Texas

Year dc:date

2007

Author dc:creator

• Parviz, Maryam

Contributors dc:contributor

• Gross, Guenter W.
• Chapman, Kent D.
• Fuchs, Jannon L.
• Gopal, Kamakshi V.
• Hynds, DiAnna
• Schwark, Harris

• neurotoxicity
• zinc toxicity
• microelectrode array
• tetrodotoxin
• Zinc -- Toxicology.
• Mice -- Effect of metals on.
• Neural networks (Neurobiology)
• Mice -- Nervous system.

Statement dc:rights

• Public
• Copyright
• Parviz, Maryam
• Copyright is held by the author, unless otherwise noted. All rights reserved.

Language dc:language

English

Identifier

oclc: 192073133
https://digital.library.unt.edu/ark:/67531/metadc3928/
ark: ark:/67531/metadc3928

OAI identifier oai:identifier

info:ark/67531/metadc3928