Pain perception in mice lacking the beta3 subunit of voltage-activated calcium channels
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.
Medienart: |
Artikel |
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Erscheinungsjahr: |
2002 |
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Erschienen: |
2002 |
Enthalten in: |
Zur Gesamtaufnahme - volume:277 |
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Enthalten in: |
The Journal of biological chemistry - 277(2002), 43 vom: 25. Okt., Seite 40342-51 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Murakami, Manabu [VerfasserIn] |
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Themen: |
Calcium Channels |
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Anmerkungen: |
Date Completed 09.12.2002 Date Revised 09.02.2021 published: Print-Electronic Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM120224658 |
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100 | 1 | |a Murakami, Manabu |e verfasserin |4 aut | |
245 | 1 | 0 | |a Pain perception in mice lacking the beta3 subunit of voltage-activated calcium channels |
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500 | |a Date Completed 09.12.2002 | ||
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500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Calcium Channels |2 NLM | |
700 | 1 | |a Fleischmann, Bernd |e verfasserin |4 aut | |
700 | 1 | |a De Felipe, Carmen |e verfasserin |4 aut | |
700 | 1 | |a Freichel, Marc |e verfasserin |4 aut | |
700 | 1 | |a Trost, Claudia |e verfasserin |4 aut | |
700 | 1 | |a Ludwig, Andreas |e verfasserin |4 aut | |
700 | 1 | |a Wissenbach, Ulrich |e verfasserin |4 aut | |
700 | 1 | |a Schwegler, Herbert |e verfasserin |4 aut | |
700 | 1 | |a Hofmann, Franz |e verfasserin |4 aut | |
700 | 1 | |a Hescheler, Jürgen |e verfasserin |4 aut | |
700 | 1 | |a Flockerzi, Veit |e verfasserin |4 aut | |
700 | 1 | |a Cavalié, Adolfo |e verfasserin |4 aut | |
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