The calcium channel α2/δ1 subunit is involved in extracellular signalling

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Abstract
The alpha2/delta1 subunit forms part of the dihydropyridine receptor, an essential protein complex for excitation-contraction (EC) coupling in skeletal muscle. Because of the lack of a viable knock-out animal, little is known regarding the role of the alpha2/delta1 subunit in EC coupling or in other cell functions. Interestingly, the alpha2/delta1 appears before the alpha1 subunit in development and contains extracellular conserved domains known to be important in cell signalling and inter-protein interactions. These facts raise the possibility that the alpha2/delta1 subunit performs vital functions not associated with EC coupling. Here, we tested the hypothesis that the alpha2/delta1 subunit is important for interactions of muscle cells with their environment. Using confocal microscopy, we followed the immunolocalization of alpha2/delta1 and alpha1 subunits with age. We found that in 2-day-old myotubes, the alpha2/delta1 subunit concentrated towards the ends of the cells, while the alpha1 subunit clustered near the centre. As myotubes aged (6-12 days), the alpha2/delta1 became evenly distributed along the myotubes and co-localized with alpha1. When the expression of alpha2/delta1 was blocked with siRNA, migration, attachment and spreading of myoblasts were impaired while the L-type calcium current remained unaffected. The results suggest a previously unidentified role of the alpha2/delta1 subunit in skeletal muscle and support the involvement of this protein in extracellular signalling. This new role of the alpha2/delta1 subunit may be crucial for muscle development, muscle repair and at times in which myoblast attachment and migration are fundamental.