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J Physiol Volume 586, Number 3, 727-738, February 1, 2008 DOI: 10.1113/jphysiol.2007.147959
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CELLULAR

The calcium channel {alpha}2/{delta}1 subunit is involved in extracellular signalling

 Kelly García1, Thomas Nabhani1 and Jesús García1

1 Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA

The {alpha}2/{delta}1 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 {alpha}2/{delta}1 subunit in EC coupling or in other cell functions. Interestingly, the {alpha}2/{delta}1 appears before the {alpha}1 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 {alpha}2/{delta}1 subunit performs vital functions not associated with EC coupling. Here, we tested the hypothesis that the {alpha}2/{delta}1 subunit is important for interactions of muscle cells with their environment. Using confocal microscopy, we followed the immunolocalization of {alpha}2/{delta}1 and {alpha}1 subunits with age. We found that in 2-day-old myotubes, the {alpha}2/{delta}1 subunit concentrated towards the ends of the cells, while the {alpha}1 subunit clustered near the centre. As myotubes aged (6–12 days), the {alpha}2/{delta}1 became evenly distributed along the myotubes and co-localized with {alpha}1. When the expression of {alpha}2/{delta}1 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 {alpha}2/{delta}1 subunit in skeletal muscle and support the involvement of this protein in extracellular signalling. This new role of the {alpha}2/{delta}1 subunit may be crucial for muscle development, muscle repair and at times in which myoblast attachment and migration are fundamental.

(Received 7 November 2007; accepted after revision 5 December 2007; first published online 6 December 2007)
Corresponding author J. García: Department of Physiology and Biophysics, University of Illinois at Chicago, 835 South Wolcott Ave, Chicago, IL 60612, USA. Email: garmar{at}uic.edu




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N. Weiss and E. Ivanova
Does the voltage-gated calcium channel {alpha}2{delta}-1 subunit play a dual function in skeletal muscle?
J. Physiol., April 15, 2008; 586(8): 2035 - 2037.
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