RYR1 and breast carcinoma: In turn, skeletal muscle ryanodine receptor 1 (RyR1) intracellular Ca2+ release channels, required for skeletal muscle excitation–contraction coupling, becomes oxidized in the setting of bone metastases, resulting in reduced muscle function.82 Skeletal muscle samples from human lung and breast cancer patients with bone metastases also exhibit evidence of RyR1 Ca2+ channel leak.