Excitation-contraction coupling is the physiological mechanism whereby an electrical signal detected by the dihydropyridine receptor, is converted into an increase in [Ca2+], via activation of ryanodine receptors. Mutations in RYR1, the gene encoding ryanodine receptor 1, are the underlying cause of various congenital myopathies including Central Core Disease, Multiminicore disease, some forms of Centronuclear myopathy and Congenital Fiber Type Disproportion. Interestingly, patients with recessive but not dominant RYR1 mutations show a significant reduction of ryanodine receptor protein in muscle biopsies as well as ophthalmoplegia. This specific involvement of the extraocular muscles indicates that this group of muscles may express different amounts of proteins involved in excitation-contraction coupling compared to limb muscles. Here we report that this is indeed the case; in particular the transcripts encoding ryanodine receptor 3, cardiac calsequestrin and the alfa 1 subunit of the cardiac dihydropyridine receptor are upregulated by at least 100 fold, while excitation coupled Ca2+ entry is three fold higher. These findings support the hypothesis that extraocular muscles have a unique mode of calcium handling.