Published in
Public Library of Science, PLoS ONE, 4(10), p. e0123762, 2015
DOI: 10.1371/journal.pone.0123762
Links
- Public Library of Science
- ORCID
- ORCID
- [www.ncbi.nlm.nih.gov] | PDF
- [opus4.kobv.de] | PDF
- [europepmc.org] | PDF
- [www.researchgate.net] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
Tools
Formalin Evokes Calcium Transients from the Endoplasmatic Reticulum
,
Kailey J. Soller,
Susanne K. Sauer,
Joanna Kalucka,
Gianluigi Veglia,
Peter W. Reeh
Full text: Download
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 for-malin 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.