Requirement of the Ca2+ channel β2 subunit for sympathetic PKA phosphorylation
Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved..
Facilitation of cardiac function in response to signals from the sympathetic nervous system is initiated by the phosphorylation of L-type voltage-dependent Ca2+ channels (VDCCs) by protein kinase A (PKA), which in turn is activated by β-adrenoceptors. Among the five subunits (α1, β, α2/δ, and γ) of VDCCs, the α1 subunit and the family of β subunits are substrates for PKA-catalyzed phosphorylation; however, the subunit responsible for β-adrenergic augmentation of Ca2+ channel function has yet to be specifically identified. Here we show that the VDCC β2 subunit is required for PKA phosphorylation upon sympathetic acceleration. In mice with β2 subunit-null mutations, cardiac muscle contraction in response to isoproterenol was reduced and there was no significant increase in Ca2+ channel currents upon PKA-dependent phosphorylation. These findings indicate that within the sympathetic nervous system the β2 subunit of VDCCs is required for physiological PKA-dependent channel phosphorylation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:145 |
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| Enthalten in: |
Journal of pharmacological sciences - 145(2021), 3 vom: 01. März, Seite 253-261 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Murakami, Manabu [VerfasserIn] |
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| Links: |
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| Themen: |
Calcium |
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| Anmerkungen: |
Date Completed 09.08.2021 Date Revised 09.08.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jphs.2020.12.011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM321612981 |
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| 100 | 1 | |a Murakami, Manabu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Requirement of the Ca2+ channel β2 subunit for sympathetic PKA phosphorylation |
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| 500 | |a Date Revised 09.08.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved. | ||
| 520 | |a Facilitation of cardiac function in response to signals from the sympathetic nervous system is initiated by the phosphorylation of L-type voltage-dependent Ca2+ channels (VDCCs) by protein kinase A (PKA), which in turn is activated by β-adrenoceptors. Among the five subunits (α1, β, α2/δ, and γ) of VDCCs, the α1 subunit and the family of β subunits are substrates for PKA-catalyzed phosphorylation; however, the subunit responsible for β-adrenergic augmentation of Ca2+ channel function has yet to be specifically identified. Here we show that the VDCC β2 subunit is required for PKA phosphorylation upon sympathetic acceleration. In mice with β2 subunit-null mutations, cardiac muscle contraction in response to isoproterenol was reduced and there was no significant increase in Ca2+ channel currents upon PKA-dependent phosphorylation. These findings indicate that within the sympathetic nervous system the β2 subunit of VDCCs is required for physiological PKA-dependent channel phosphorylation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Calcium | |
| 650 | 4 | |a Channel | |
| 650 | 4 | |a Mouse | |
| 650 | 4 | |a Phosphorylation | |
| 650 | 7 | |a Calcium Channels, L-Type |2 NLM | |
| 650 | 7 | |a Receptors, Adrenergic, beta |2 NLM | |
| 650 | 7 | |a Cyclic AMP-Dependent Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.11 |2 NLM | |
| 650 | 7 | |a Isoproterenol |2 NLM | |
| 650 | 7 | |a L628TT009W |2 NLM | |
| 700 | 1 | |a Xu, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Ohba, Takayoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Takeshi |e verfasserin |4 aut | |
| 700 | 1 | |a Inoue, Yoshiro |e verfasserin |4 aut | |
| 700 | 1 | |a Murakami, Agnieszka M |e verfasserin |4 aut | |
| 700 | 1 | |a Miyoshi, Ichiro |e verfasserin |4 aut | |
| 700 | 1 | |a Ono, Kyoichi |e verfasserin |4 aut | |
| 700 | 1 | |a Tohse, Noritsugu |e verfasserin |4 aut | |
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