Oligomerisation of Ca2+-regulatory membrane components involved in the excitation-contraction-relaxation cycle during postnatal development of rabbit skeletal muscle.

The skeletal muscle excitation-contraction-relaxation cycle matures during the first weeks after birth and protein-protein interactions are believed to be essential for proper Ca2+ regulation. We therefore studied potential changes in the oligomerisation of key components of the Ca2+-regulatory membrane system during postnatal myogenesis. In contrast to a decrease in calreticulin, the Ca2+-binding proteins calsequestrin and sarcalumenin increased in abundance in microsomes isolated from muscle between postnatal days 1 and 41. While the expression of the fast Ca2+-ATPase increased, its slow-twitch isoform decreased. The junctional component triadin, the 53 kDa sarcoplasmic reticulum glycoprotein, as well as the dihydropyridine receptor increased in abundance, while no major changes in the expression of the ryanodine receptor were observed. Crosslinking analysis revealed that the fast Ca2+-ATPase, alpha1-dihydropyridine receptor and calsequestrin exhibit a more pronounced tendency to oligomerise in adult muscle fibres as compared to early postnatal stages. Interestingly, adult calsequestrin exists not only as a 63 kDa form but also as stable molecular species of higher molecular mass. These findings imply that during postnatal development, protein-protein interactions within the Ca2+-regulatory membrane system become more complex and oligomerisation appears to be an essential prerequisite for the proper physiological functioning of key membrane proteins in matured skeletal muscle fibres.