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. 2012 Nov 17;28(6):715–722. doi: 10.1007/s12264-012-1284-9

Formaldehyde increases intracellular calcium concentration in primary cultured hippocampal neurons partly through NMDA receptors and T-type calcium channels

Ye-Nan Chi 1, Xu Zhang 1, Jie Cai 1, Feng-Yu Liu 1, Guo-Gang Xing 2, You Wan 1,2,✉
PMCID: PMC5561821  PMID: 23160928

Abstract

Objective

Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. Formaldehyde induces mis-folding and aggregation of neuronal tau protein, hippocampal neuronal apoptosis, cognitive impairment and loss of memory functions, as well as excitation of peripheral nociceptive neurons in cancer pain models. Intracellular calcium ([Ca2+]i) is an important intracellular messenger, and plays a key role in many pathological processes. The present study aimed to investigate the effect of formaldehyde on [Ca2+]i and the possible involvement of N-methyl-D-aspartate receptors (NMDARs) and T-type Ca2+ channels on the cell membrane.

Methods

Using primary cultured hippocampal neurons as a model, changes of [Ca2+]i in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy.

Results

Formaldehyde at 1 mmol/L approximately doubled [Ca2+]i. (2R)-amino-5-phosphonopentanoate (AP5, 25 μmol/L, an NMDAR antagonist) and mibefradil (MIB, 1 μmol/L, a T-type Ca2+ channel blocker), given 5 min after formaldehyde perfusion, each partly inhibited the formaldehyde-induced increase of [Ca2+]i, and this inhibitory effect was reinforced by combined application of AP5 and MIB. When applied 3 min before formaldehyde perfusion, AP5 (even at 50 μmol/L) did not inhibit the formaldehyde-induced increase of [Ca2+]i, but MIB (1 μmol/L) significantly inhibited this increase by 70%.

Conclusion

These results suggest that formaldehyde at a low concentration increases [Ca2+]i in cultured hippocampal neurons; NMDARs and T-type Ca2+ channels may be involved in this process.

Keywords: formaldehyde, intracellular calcium, neuronal activation, NMDA receptors, T-type calcium channels

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