Cardiac L-type calcium channel (Cav1.2) associates with subunits

The cardiac voltage-gated Ca channel, Cav1.2, mediates excitation-contraction coupling in the heart. The molecular composition of the channel includes the pore-forming 1 subunit and auxiliary 2/ -1 and subunits. Ca channel subunits, of which there are 8 isoforms, consist of 4 transmembrane domains with intracellular Nand C-terminal ends. The 1 subunit was initially detected in the skeletal muscle Cav1.1 channel complex, modulating current amplitude and activation and inactivation properties. The 1 subunit also shifts the steady-state inactivation to more negative membrane potentials, accelerates current inactivation, and increases peak currents, when coexpressed with the cardiac 1c subunit in Xenopus oocytes and human embryonic kidney (HEK) 293 cells. The 1 subunit is not expressed, however, in cardiac muscle. We sought to determine whether subunits that are expressed in cardiac tissue physically associate with and modulate Cav1.2 function. We now demonstrate that 4, 6, 7, and 8 subunits physically interact with the Cav1.2 complex. The subunits differentially modulate Ca channel function when coexpressed with the 1b and 2/ -1 subunits in HEK cells, altering both activation and inactivation properties. The effects of on Cav1.2 function are dependent on the subtype of subunit. Our results identify new members of the cardiac Cav1.2 macromolecular complex and identify a mechanism by which to increase the functional diversity of Cav1.2 channels.—Yang, L., Katchman, A., Morrow, J. P., Doshi, D., Marx, S. A. Cardiac L-type calcium channel (CaV1.2) associates with subunits. FASEB J. 25, 000 – 000 (2010). www.fasebj.org