Pain perception in mice lacking the beta3 subunit of voltage-activated calcium channels
| Autor: | Manabu Murakami, Andreas Ludwig, Franz Hofmann, Marc Freichel, Jürgen Hescheler, Bernd K. Fleischmann, Veit Flockerzi, Ulrich Wissenbach, Claudia Trost, Carmen De Felipe, Herbert Schwegler, Adolfo Cavalié |
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| Přispěvatelé: | German Research Foundation |
| Rok vydání: | 2002 |
| Předmět: |
Male
P-type calcium channel Patch-Clamp Techniques Protein subunit Pain Biochemistry Mice Dorsal root ganglion medicine Animals Amino Acid Sequence Molecular Biology Evoked Potentials Neurons Voltage-dependent calcium channel Chemistry Calcium channel T-type calcium channel Cell Biology Anatomy Cell biology R-type calcium channel medicine.anatomical_structure Nociception Spinal Cord Sensory Thresholds Calcium Channels Ion Channel Gating |
| Zdroj: | The Journal of biological chemistry. 277(43) |
| ISSN: | 0021-9258 |
| Popis: | 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 α1B subunit (N-type). The accessory β3 subunits of calcium channels are preferentially associated with the α1B subunit in neurones. Here we show that deletion of the β3 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 cordin 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 β3 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 (α1B) and functional alterations of calcium channel currents in neurones projecting to the spinal cord. ThisstudywassupportedbygrantsfromtheDeutscheForschungsgemeinschaftandFondsderChemie(toV.F.). |
| Databáze: | OpenAIRE |
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