Altered nociceptive response in mice deficient in the alpha(1B) subunit ofthe voltage-dependent calcium channel

Citation
C. Kim et al., Altered nociceptive response in mice deficient in the alpha(1B) subunit ofthe voltage-dependent calcium channel, MOL CELL NE, 18(2), 2001, pp. 235-245
Citations number
59
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR AND CELLULAR NEUROSCIENCE
ISSN journal
1044-7431 → ACNP
Volume
18
Issue
2
Year of publication
2001
Pages
235 - 245
Database
ISI
SICI code
1044-7431(200108)18:2<235:ANRIMD>2.0.ZU;2-U
Abstract
Calcium influx through N-type calcium channels mediates synaptic transmissi on at numerous central synapses and transduces nociceptive information in t he spinal dorsal hom. However, the precise role of N-type calcium channels in pain perception is not fully elucidated. To address this issue, we gener ated and analyzed knockout mice for a,,, the pore-forming subunit of the N- type calcium channel. Homozygous mutants are viable, fertile, and show norm al motor coordination. In small-diameter dorsal root ganglion neurons from mutants the density of calcium channel currents is significantly reduced, w hich can be accounted for by the abolition of N-type currents. We performed several pain-related behavioral tests using the mutant mice. alpha (1B)-De ficient mice show reduced response to mechanical stimuli in the von Frey te st and increased tail flick latency in response to radiant heat, indicating altered spinal reflexes. However, pain response in the hot plate test is n ormal. In the formalin paw test, the mutant mice exhibit significantly atte nuated response in Phase 2, but normal pain behaviors in Phase 1. The respo nse to visceral inflammatory pain caused by acetic acid is also reduced in alpha (1B) knockout mice. These results suggest that the alpha (1B) subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level.