Fig. 6. Model for superior Ca²⁺ homeostasis in EOM.

Schematic (A) shows an EOM muscle cell with a larger SR, numerous pumps and transporters in both the sarcolemma and the sarcoplasmic membrane and many Ca²⁺ binding proteins in the cytosol (e.g. S100a, Parv) and SR (Casq1 and Casq2), as well as numerous mitochondria. CamkII phosphorylates Pln at Thr17, which regulates Serca2. Schematic (B) represents a TA muscle cell containing a smaller SR, fewer pumps and transporters and less Ca²⁺ binding proteins in the cytosol and SR compared with EOM. Excess Ca²⁺ ions entering the cell can be bound and/or removed more effectively in EOM than TA, leading to a faster return to resting Ca²⁺ levels. We propose that the extensive Ca²⁺ handling capacity of EOM reflects their functional properties and may help to protect this muscle group from Ca²⁺ mediated damage in DMD. (Symbols: Serca: sarcoplasmic reticulum Ca²⁺-ATPase, Casq: Calsequestrin, Pln: Phospholamban, Pmca: plasmamembrane Ca²⁺-ATPase, Parv: Parvalbumin, CamkII: Ca²⁺/Calmodulin dependent kinase II, Calm: Calmodulin, Mito: Mitochondria, Ncx: Na⁺/Ca²⁺-exchanger, Thr17-P: phosphorylated threonine 17 residue).