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

doi:10.1371/journal.pone.0123762

Formalin evokes calcium transients from the endoplasmatic reticulum

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

Authors

Michael J M Fischer¹, Kailey J Soller², Susanne K Sauer¹, Joanna Kalucka³, Gianluigi Veglia⁴, Peter W Reeh¹

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism*
Calcium Signaling
Endoplasmic Reticulum / drug effects*
Endoplasmic Reticulum / metabolism
Formaldehyde / pharmacology*
Ganglia, Spinal / cytology
Ganglia, Spinal / drug effects*
Ganglia, Spinal / metabolism
Gene Expression Regulation
HEK293 Cells
Humans
Keratinocytes / cytology
Keratinocytes / drug effects
Keratinocytes / metabolism
Membrane Potentials / drug effects
Membrane Potentials / physiology
Mice
Mice, Inbred C57BL
Pain / chemically induced
Pain / genetics
Pain / metabolism*
Pain / physiopathology
Pain Measurement
Patch-Clamp Techniques
Primary Cell Culture
Rabbits
Rats
Rats, Wistar
Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics
Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*
Sensory Receptor Cells / cytology
Sensory Receptor Cells / drug effects*
Sensory Receptor Cells / metabolism
TRPA1 Cation Channel
Transient Receptor Potential Channels / genetics
Transient Receptor Potential Channels / metabolism

Substances

TRPA1 Cation Channel
Transient Receptor Potential Channels
Trpa1 protein, mouse
Formaldehyde
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding