Cardiac calcium handling in the mouse model of Duchenne Muscular Dystrophy

摘要: The dystrophinopathies are a group of disorders characterised by cellular absence the membrane stabilising protein, dystrophin. Duchenne muscular dystrophy is most severe disorder clinically. deficiency dystrophin, in X-linked (mdx) mouse causes an elevation intracellular calcium cardiac myocytes. Potential mechanisms contributing to increased include enhanced influx, sarcoplasmic reticular release and\or reduced sequestration or sarcolemmal efflux. This dissertation examined potential that may contribute overload murine model dystrophy. general cardiomyopathy mdx myocardium was evident, with left atria from consistently producing less force than control atria. associated delayed relaxation. role L-type channels mediating influx initially investigated. Dihydropyridines had lower potency contracting corresponding redued dihydropyridine receptor affinity radioligand binding studies ventricular homogenates (P<0.05). protein and mRNA levels function reticulum terms also via sarco-endoplasmic ATPase were A contraction evident response range stimulation frequencies (P<0.05) concentrations extracellular However, presence 1 nM Ryanodine block release, frequency caused similar forces those obtained mice suggesting mdx. Rapid cooling contractures showed contracture compared cooling. suggests some dysfunction SR storage, which be relaxation time. Concentration-response curves inhibitors no difference enzyme responsible for uptake into reticulum. Although upregulated, functional benefit evident. study indicates dystrophin leads upregulation change sequestration. Upregulation pathway mechanism observed muscle.