title: Pain perception in mice lacking the beta3 subunit of voltage-activated calcium channels.
abstract: 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 alpha1B subunit (N-type). The accessory beta3 subunits of calcium channels are preferentially associated with the alpha1B subunit in neurones. Here we show that deletion of the beta3 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 beta3 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 (alpha1B) and functional alterations of calcium channel currents in neurones projecting to the spinal cord.
authors.affiliation: Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany.
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.forename: Bernd
authors.initials: B
authors.lastname: Fleischmann
authors.forename: Carmen
authors.initials: C
authors.lastname: De Felipe
authors.forename: Marc
authors.initials: M
authors.lastname: Freichel
authors.forename: Claudia
authors.initials: C
authors.lastname: Trost
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wissenbach
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwegler
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Veit
authors.initials: V
authors.lastname: Flockerzi
authors.forename: Adolfo
authors.initials: A
authors.lastname: Cavalié
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005071:Evoked Potentials; D015640:Ion Channel Gating; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D012684:Sensory Thresholds; D013116:Spinal Cord / Q000503:physiopathology
chemical_list: D015220:Calcium Channels