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Mechanical ventilation causes Ca2+ disruptions that lead to increased proteolysis. ROS production from mitochondria, along with increased protein kinase A (PKA) activity, modify ryanodine receptors (RyR1) leading to the disassociation of calstabin-1. Disassociation of calstabin-1 from RyR1 leads to Ca2+ leak, activation of calpains, and increased proteolysis that contributes to VIDD.
