Cardiac CaV1.2 channels require &bgr; subunits for &bgr;-adrenergic–mediated modulation but not trafficking

Ca2+ channel &bgr;-subunit interactions with pore-forming &agr;-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 &agr;1C subunits lacking capacity to bind CaV&bgr; can traffic to the sarcolemma in adult cardiomyocytes in vivo and sustain normal excitation-contraction coupling. However, these &bgr;-less Ca2+ channels cannot be stimulated by &bgr;-adrenergic pathway agonists, and thus adrenergic augmentation of contractility is markedly impaired in isolated cardiomyocytes and in hearts. Similarly, viral-mediated expression of a &bgr;-subunit–sequestering peptide sharply curtailed &bgr;-adrenergic stimulation of WT Ca2+ channels, identifying an approach to specifically modulate &bgr;-adrenergic regulation of cardiac contractility. Our data demonstrate that &bgr; subunits are required for &bgr;-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.