The calcium channel α2/δ1 subunit interacts with ATP5b in the plasma membrane of developing muscle cells.

The α2/δ1 and α(1)1.1 subunits are present at a 1:1 ratio in the dihydropyridine receptor (DHPR) from adult skeletal muscle. In contrast, during early myotube development α2/δ1 is present at higher levels than α(1)1.1 and localizes at the ends of the cells, suggesting that α2/δ1 may have a role independent from DHPRs. We sought to identify binding partners of α2/δ1 at a period when levels of α(1)1.1 are low. Analysis of protein complexes in their native configuration established that α2/δ1 may be associating with ATP5b, a subunit of a mitochondrial ATP synthase complex. This interaction was confirmed with fluorescence resonance energy transfer and coimmunoprecipitation. The association of α2/δ1 and ATP5b occurs in intracellular membranes and at the plasma membrane, where they form a functional signaling complex capable of accelerating the rate of decline of calcium transients. The acceleration of decay was more evident when myotubes were stimulated with a train of pulses. Our data indicate that the α2/δ1 subunit is not only part of the DHPR but that it may interact with other cellular components in developing myotubes, such as the ATP5b in its atypical localization in the plasma membrane.