| First Author | Lee A | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 3 | Pages | 1505-21 |
| PubMed ID | 25468907 | Mgi Jnum | J:218379 |
| Mgi Id | MGI:5617403 | Doi | 10.1074/jbc.M114.607465 |
| Citation | Lee A, et al. (2015) Characterization of Cav1.4 Complexes (alpha11.4, beta2, and alpha2delta4) in HEK293T Cells and in the Retina. J Biol Chem 290(3):1505-21 |
| abstractText | In photoreceptor synaptic terminals, voltage-gated Cav1.4 channels mediate Ca(2+) signals required for transmission of visual stimuli. Like other high voltage-activated Cav channels, Cav1.4 channels are composed of a main pore-forming Cav1.4 alpha1 subunit and auxiliary beta and alpha2delta subunits. Of the four distinct classes of beta and alpha2delta, beta2 and alpha2delta4 are thought to co-assemble with Cav1.4 alpha1 subunits in photoreceptors. However, an understanding of the functional properties of this combination of Cav subunits is lacking. Here, we provide evidence that Cav1.4 alpha1, beta2, and alpha2delta4 contribute to Cav1.4 channel complexes in the retina and describe their properties in electrophysiological recordings. In addition, we identified a variant of beta2, named here beta2X13, which, along with beta2a, is present in photoreceptor terminals. Cav1.4 alpha1, beta2, and alpha2delta4 were coimmunoprecipitated from lysates of transfected HEK293 cells and mouse retina and were found to interact in the outer plexiform layer of the retina containing the photoreceptor synaptic terminals, by proximity ligation assays. In whole-cell patch clamp recordings of transfected HEK293T cells, channels (Cav1.4 alpha1 + beta2X13) containing alpha2delta4 exhibited weaker voltage-dependent activation than those with alpha2delta1. Moreover, compared with channels (Cav1.4 alpha1 + alpha2delta4) with beta2a, beta2X13-containing channels exhibited greater voltage-dependent inactivation. The latter effect was specific to Cav1.4 because it was not seen for Cav1.2 channels. Our results provide the first detailed functional analysis of the Cav1.4 subunits that form native photoreceptor Cav1.4 channels and indicate potential heterogeneity in these channels conferred by beta2a and beta2X13 variants. |
