A patient with Duchenne muscular dystrophy lacks dystrophin. Which biomechanical consequence directly causes membrane fragility and progressive myofiber death?
- A Loss of the dystrophin-glycoprotein complex linking actin cytoskeleton to the extracellular matrix, causing sarcolemmal tears during contraction-induced shear stress ✓
- B Absence of dystrophin impairs titin anchoring, causing passive elastic tension failure during relaxation
- C Reduced dystrophin causes calcium pump (SERCA) downregulation, allowing Ca2+ overload and protease activation
- D Dystrophin deficiency reduces acetylcholine receptor clustering at NMJ causing functional denervation
Explanation
Dystrophin is a subsarcolemmal protein that anchors F-actin to the dystrophin-glycoprotein complex (DGC), which in turn links to laminin in the extracellular matrix. This provides mechanical reinforcement of the sarcolemma during contractile force generation. Without dystrophin, the mechanical link is absent — during muscle contraction, lateral shear forces tear the sarcolemma, creating microlesions. Ca2+ influx through these tears activates calpains and triggers myofiber necrosis. This is repeated with each contraction cycle, eventually exhausting regenerative capacity. Options B and C are secondary consequences; option D is not a mechanism of muscular dystrophy.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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Written and medically reviewed by the StethoPrep medical team.