Figure 6.

Schematic model of intracellular mechanisms underlying muscle weakness in arthritis. nNOS is globally increased in arthritic muscle and more nNOS is bound to the RyR1 protein complex. This leads to RNS-induced modifications of the RyR1 protein complex and the SR Ca²⁺ release during contractions increases, which further activates the Ca²⁺-sensitive nNOS and RNS production is augmented. The increased amounts of RNS attack myofibrillar proteins, such as actin, and cause contractile dysfunction and muscle weakness.