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Originally published In Press as doi:10.1074/jbc.M203425200 on August 2, 2002
J. Biol. Chem., Vol. 277, Issue 43, 40342-40351, October 25, 2002
Pain Perception in Mice Lacking the 3 Subunit of
Voltage-activated Calcium Channels*
Manabu
Murakami §,
Bernd
Fleischmann¶,
Carmen
De
Felipe ,
Marc
Freichel ,
Claudia
Trost ,
Andreas
Ludwig**,
Ulrich
Wissenbach ,
Herbert
Schwegler ,
Franz
Hofmann**,
Jürgen
Hescheler¶,
Veit
Flockerzi , and
Adolfo
Cavalié §§
From the Pharmakologie und Toxikologie,
Universität des Saarlandes, D-66421 Homburg, Germany,
§ Molecular Pharmacology, Tohoku University School of
Medicine, Sendai 980, Japan, ¶ Institut für
Neurophysiologie, Universität zu Köln, D-50931 Köln,
Germany, Instituto de Neurosciencias, Universidad Miguel
Hernandez, 03550 San Juan de Alicante, Spain, ** Institut
für Pharmakologie und Toxikologie, TU München, D-80802
München, Germany,  Institut für
Anatomie, Universität Magdeburg, D-39120 Magdeburg, Germany
The importance of voltage-activated calcium
channels in pain processing has been suggested by the spinal
antinociceptive action of blockers of N- and P/Q-type calcium channels
as well as by gene targeting of the 1B subunit (N-type). The
accessory 3 subunits of calcium channels are preferentially
associated with the 1B subunit in neurones. Here we show that
deletion of the 3 subunit by gene targeting affects strongly the
pain processing of mutant mice. We pinpoint this defect in the
pain-related behavior and ascending pain pathways of the spinal cord
in vivo and at the level of calcium channel currents and
proteins in single dorsal root ganglion neurones in vitro.
The pain induced by chemical inflammation is preferentially damped by
deletion of 3 subunits, whereas responses to acute thermal and
mechanical harmful stimuli are reduced moderately or not at all,
respectively. The defect results in a weak wind-up of spinal cord
activity during intense afferent nerve stimulation. The molecular
mechanism responsible for the phenotype was traced to low expression of
N-type calcium channels ( 1B) and functional alterations of calcium
channel currents in neurones projecting to the spinal cord.
*
This study was supported by grants from the Deutsche
Forschungsgemeinschaft and Fonds der Chemie (to V. F.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
§§
To whom correspondence should be addressed. Tel.:
49-6841-1626151; Fax: 49-6841-1626402; E-mail:
adolfo.cavalie@uniklinik-saarland.de.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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