title: Formaldehyde increases intracellular calcium concentration in primary cultured hippocampal neurons partly through NMDA receptors and T-type calcium channels.
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 ([Ca(2+)](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 [Ca(2+)](i) and the possible involvement of N-methyl-D-aspartate receptors (NMDARs) and T-type Ca(2+) channels on the cell membrane.
  
  
  METHODS
  Using primary cultured hippocampal neurons as a model, changes of [Ca(2+)](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 [Ca(2+)](i). (2R)-amino-5-phosphonopentanoate (AP5, 25 μmol/L, an NMDAR antagonist) and mibefradil (MIB, 1 μmol/L, a T-type Ca(2+) channel blocker), given 5 min after formaldehyde perfusion, each partly inhibited the formaldehyde-induced increase of [Ca(2+)](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 [Ca(2+)](i), but MIB (1 μmol/L) significantly inhibited this increase by 70%.
  
  
  CONCLUSIONS
  These results suggest that formaldehyde at a low concentration increases [Ca(2+)](i) in cultured hippocampal neurons; NMDARs and T-type Ca(2+) channels may be involved in this process.
authors.affiliation: Neuroscience Research Institute and Department of Neurobiology, Peking University, Beijing 100191, China.
authors.forename: Ye-Nan
authors.initials: YN
authors.lastname: Chi
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.forename: Feng-Yu
authors.initials: FY
authors.lastname: Liu
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Xing
authors.forename: You
authors.initials: Y
authors.lastname: Wan
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020748:Mibefradil / Q000494:pharmacology; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde; D020748:Mibefradil; D015763:2-Amino-5-phosphonovalerate; D002118:Calcium