| First Author | Yang L | Year | 2011 |
| Journal | FASEB J | Volume | 25 |
| Issue | 3 | Pages | 928-36 |
| PubMed ID | 21127204 | Mgi Jnum | J:262599 |
| Mgi Id | MGI:6164122 | Doi | 10.1096/fj.10-172353 |
| Citation | Yang L, et al. (2011) Cardiac L-type calcium channel (Cav1.2) associates with gamma subunits. FASEB J 25(3):928-36 |
| abstractText | 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 alpha1 subunit and auxiliary alpha2/delta-1 and beta subunits. Ca(2+) channel gamma subunits, of which there are 8 isoforms, consist of 4 transmembrane domains with intracellular N- and C-terminal ends. The gamma1 subunit was initially detected in the skeletal muscle Ca(v)1.1 channel complex, modulating current amplitude and activation and inactivation properties. The gamma1 subunit also shifts the steady-state inactivation to more negative membrane potentials, accelerates current inactivation, and increases peak currents, when coexpressed with the cardiac alpha1c subunit in Xenopus oocytes and human embryonic kidney (HEK) 293 cells. The gamma1 subunit is not expressed, however, in cardiac muscle. We sought to determine whether gamma subunits that are expressed in cardiac tissue physically associate with and modulate Ca(v)1.2 function. We now demonstrate that gamma4, gamma6, gamma7, and gamma8 subunits physically interact with the Ca(v)1.2 complex. The gamma subunits differentially modulate Ca(2+) channel function when coexpressed with the beta1b and alpha2/delta-1 subunits in HEK cells, altering both activation and inactivation properties. The effects of gamma on Ca(v)1.2 function are dependent on the subtype of beta 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. |
