Cardiac CaV1.2 channels require ß subunits for ß-adrenergic-mediated modulation but not trafficking.
J Clin Invest
; 129(2): 647-658, 2019 02 01.
Article
em En
| MEDLINE
| ID: mdl-30422117
ABSTRACT
Ca2+ channel ß-subunit interactions with pore-forming α-subunits are long-thought to be obligatory for channel trafficking to the cell surface and for tuning of basal biophysical properties in many tissues. Unexpectedly, we demonstrate that transgenic expression of mutant α1C subunits lacking capacity to bind CaVß can traffic to the sarcolemma in adult cardiomyocytes in vivo and sustain normal excitation-contraction coupling. However, these ß-less Ca2+ channels cannot be stimulated by ß-adrenergic pathway agonists, and thus adrenergic augmentation of contractility is markedly impaired in isolated cardiomyocytes and in hearts. Similarly, viral-mediated expression of a ß-subunit-sequestering peptide sharply curtailed ß-adrenergic stimulation of WT Ca2+ channels, identifying an approach to specifically modulate ß-adrenergic regulation of cardiac contractility. Our data demonstrate that ß subunits are required for ß-adrenergic regulation of CaV1.2 channels and positive inotropy in the heart, but are dispensable for CaV1.2 trafficking to the adult cardiomyocyte cell surface, and for basal function and excitation-contraction coupling.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sarcolema
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Canais de Cálcio Tipo L
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Miócitos Cardíacos
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2019
Tipo de documento:
Article