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

ABSTRACT: The cardiac voltage-gated Ca(2+) channel, Ca(v)1.2, 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(2+) channel ? subunits, of which there are 8 isoforms, consist of 4 transmembrane domains with intracellular N- and C-terminal ends. The ?1 subunit was initially detected in the skeletal muscle Ca(v)1.1 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 Ca(v)1.2 function. We now demonstrate that ?4, ?6, ?7, and ?8 subunits physically interact with the Ca(v)1.2 complex. The ? subunits differentially modulate Ca(2+) channel function when coexpressed with the ?1b and ?2/?-1 subunits in HEK cells, altering both activation and inactivation properties. The effects of ? on Ca(v)1.2 function are dependent on the subtype of ? subunit. Our results identify new members of the cardiac Ca(v)1.2 macromolecular complex and identify a mechanism by which to increase the functional diversity of Ca(v)1.2 channels.

SUBMITTER: Yang L 

PROVIDER: S-EPMC3042847 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature