Figure 9.

Pathway of skeletal muscle inhibition via Nav1.4. This is a cartoon representation of the mechanism and pathway through which CBD inhibits Nav1.4. Once CBD is exposed to the skeletal muscle, given its high lipophilicity, the majority of it gets inside the sarcolemma. Upon entering the sarcolemma, it localizes in the middle regions of the leaflet and travels through the Nav1.4 fenestrations into the pore. Inside the pore mutation of the LA, F1586A reduces CBD inhibition. CBD also alters the membrane elasticity, which promotes the inactivated state of the Nav channel, which adds to the overall CBD inhibitory effects. The net result is a reduced electrical excitability of the skeletal muscle, which, at least in part, contributes to a reduction in muscle contraction.

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