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Research was conducted to examine the hypothesis that apocalmodulin and Ca2+ calmodulin bind to the same region on the skeletal muscle Ca2+ release channel. The ability of calmodulin (CaM) to protect its binding site from tryptic inactivation was used to localize the CaM binding site on ryanodine receptor (RYR1). Results suggest that both Ca2+ CaM and apocalmodulin bind to the same or overlapping regions on RYR1 and block access of trypsin to sites at amino acids 3630 and 3637.

A study of skeletal muscle Ca2+ release channel (RyR1) during oxidation showed that some features of the RyR1 sites for binding apocalmodulin are distinct from those of the Ca2+/calmodulin site. Results also revealed that oxidation can change the activity of RyR1 by changing its interaction with calmodulin. Moreover, calmodulin was found to be capable of protecting RyR1 from oxidative modifications during periods of oxidative stress.

The effects of an amino acid present in the cardiac and skeletal Ca2+ channel alpha1-subunits on the activity of the Ca2+-release channel and its ability to bind [3H]ryanodine were analyzed in planar lipid bilayers. The synthetic peptide which represented the carboxy-terminal region of the dihydropyridine alpha1-subunit inhibited [3H]ryanodine binding to skeletal and cardiac sarcoplasmic reticulum (SR) membranes. Furthermore, the synthetic peptide inhibited the activity of the SR Ca2+-release channels that were reconstituted into lipid bilayers.