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PLoS One. 2015 Apr 15;10(4):e0123762. doi: 10.1371/journal.pone.0123762. eCollection 2015.

Formalin evokes calcium transients from the endoplasmatic reticulum.

Author information

1
Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Germany.
2
Department of Chemistry, University of Minnesota, Minneapolis, United States of America.
3
VIB Vesalius Research Center, Campus Gasthuisberg, KU Leuven, Leuven, Belgium.
4
Department of Chemistry, University of Minnesota, Minneapolis, United States of America; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United States of America.

Abstract

The formalin test is the most widely used behavioral screening test for analgesic compounds. The cellular mechanism of action of formaldehyde, inducing a typically biphasic pain-related behavior in rodents is addressed in this study. The chemoreceptor channel TRPA1 was suggested as primary transducer, but the high concentrations used in the formalin test elicit a similar response in TRPA1 wildtype and knockout animals. Here we show that formaldehyde evokes a dose-dependent calcium release from intracellular stores in mouse sensory neurons and primary keratinocytes as well as in non-neuronal cell lines, and independent of TRPA1. The source of calcium is the endoplasmatic reticulum and inhibition of the sarco/endoplasmic reticulum calcium-ATPase has a major contribution. This TRPA1-independent mechanism may underlie formaldehyde-induced pan-neuronal excitation and subsequent inflammation.

PMID:
25875358
PMCID:
PMC4398422
DOI:
10.1371/journal.pone.0123762
[Indexed for MEDLINE]
Free PMC Article

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