FUNCTIONAL ALTERATIONS IN SARCOPLASMIC-RETICULUM MEMBRANES OF MAGNESIUM-DEFICIENT RAT SKELETAL-MUSCLE AS CONSEQUENCES OF FREE RADICAL-MEDIATED PROCESS

Free radical-induced physiopathologies are generally thought to be med iated by membrane injuries. Using a pro-oxidant model induced by dieta ry magnesium deficiency, we have recently shown that skeletal muscle l esions occurred with a rise in the calcium level and enhanced free rad ical production. In this study, we investigated the physicochemical an d biochemical properties of sarcoplasmic reticulum membranes isolated from hind limb muscles of weanling male rats pair fed magnesium-defici ent or control diets for 12 d. The calcium-induced calcium efflux from preloaded vesicles was increased in membranes isolated from Mg-defici ent rat muscle. In agreement with this latter observation, we demonstr ated increased ryanodine binding affinity of the calcium channel. The Ca2+-ATPase activity of the pump was shown to be reduced. The viscosit y state of the membranes, assessed by 1,6-diphenyl-1,3,5-hexatriene fl uorescence anisotropy, was significantly increased in Mg-deficient mem branes. Moreover, these membranes demonstrated an increased content of protein carbonyls as compared with controls. These functional as well as structural changes are closed to those described in sarcoplasmic r eticulum membranes oxidatively modified in vitro. Together, these data fitted well with the concept that free radical-induced membrane damag es resulting in calcium overload may be at the origine of skeletal mus cle lesion during Mg-deficiency.