| Autor: |
Manabu Murakami, Feng Xu, Takayoshi Ohba, Takeshi Kobayashi, Yoshiro Inoue, Agnieszka M. Murakami, Ichiro Miyoshi, Kyoichi Ono, Noritsugu Tohse |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Journal of Pharmacological Sciences, Vol 145, Iss 3, Pp 253-261 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1016/j.jphs.2020.12.011 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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