| First Author | Yang L | Year | 2019 |
| Journal | J Clin Invest | Volume | 129 |
| Issue | 2 | Pages | 647-658 |
| PubMed ID | 30422117 | Mgi Jnum | J:287220 |
| Mgi Id | MGI:6391889 | Doi | 10.1172/JCI123878 |
| Citation | Yang L, et al. (2019) Cardiac CaV1.2 channels require beta subunits for beta-adrenergic-mediated modulation but not trafficking. J Clin Invest 129(2):647-658 |
| abstractText | Ca2+ channel beta-subunit interactions with pore-forming alpha-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 alpha1C subunits lacking capacity to bind CaVbeta can traffic to the sarcolemma in adult cardiomyocytes in vivo and sustain normal excitation-contraction coupling. However, these beta-less Ca2+ channels cannot be stimulated by beta-adrenergic pathway agonists, and thus adrenergic augmentation of contractility is markedly impaired in isolated cardiomyocytes and in hearts. Similarly, viral-mediated expression of a beta-subunit-sequestering peptide sharply curtailed beta-adrenergic stimulation of WT Ca2+ channels, identifying an approach to specifically modulate beta-adrenergic regulation of cardiac contractility. Our data demonstrate that beta subunits are required for beta-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. |
