Formalin evokes calcium transients from the endoplasmatic reticulum

Michael J.M. Fischer, Kailey J. Soller, Susanne K. Sauer, Joanna Kalucka, Gianluigi Veglia, Peter W. Reeh

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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.

Original languageEnglish (US)
Article numbere0123762
JournalPloS one
Volume10
Issue number4
DOIs
StatePublished - Apr 15 2015

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    Fischer, M. J. M., Soller, K. J., Sauer, S. K., Kalucka, J., Veglia, G., & Reeh, P. W. (2015). Formalin evokes calcium transients from the endoplasmatic reticulum. PloS one, 10(4), [e0123762]. https://doi.org/10.1371/journal.pone.0123762