Calcium Transport Inhibition, Stimulation, and Light Dependent Modulation of the Skeletal Calcium Release Channel (RyR1) by the Prototropic Forms of Pelargonidin

摘要

The principle calcium regulator in the muscle cell is the calcium ion release channel (RyR). Improper calcium homeostasis in the muscle cell is the foundation of many pathological states and has been targeted as a contributing factor to ventricular tachycardia, which is known to precede sudden cardiac arrest.Numerous endogenous and exogenous compounds can affect the way RyR regulates calcium. In this study the anthocyanidin Pelargonidin (Pg), an important natural colorant and dietary antioxidant, is evaluated for its effect on regulating the transport of calcium through the RyR1 of skeletal muscle sarcoplasmic reticulum. Pelargonidin undergoes time dependent structural changes in aqueous solutions at physiological pH and a mixture of up to seven forms of Pelargonidin are present in solution simultaneously. Pelargonidin is a unique RyR1 modulator. It can both stimulate and inhibit the RyR1 depending on the experimental conditions. In addition, when Pelargonidin is irradiated with white light, its inhibition properties on the RyR1 are essentially nullified. Proposed mechanisms include excited state charge shift within RyR1-Pg complexes.