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Basis of Muscle Dysfunction in RYR1-related Myopathies

Basis of Muscle Dysfunction in RYR1-related MyopathiesThe type I ryanodine receptor (RYR1) encodes a calcium-permeable channel in the sarcoplasmic reticulum of skeletal muscle that is responsible to releasing calcium during excitation-contraction coupling used to drive muscle contraction. Mutations in the RYR1 gene underlie several debilitating, life-threatening muscle diseases.

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Role of Store-operated Calcium Entry in Skeletal Muscle

Role of Store-operated Calcium Entry in Skeletal MuscleOur group was the first to demonstrate that store-operated Ca2+ entry (SOCE) in skeletal muscle cells is coordinated by both STIM1 Ca2+ sensors located in the sarcoplasmic reticulum and Ca2+-permeable Orai1 channels in the sarcolemma. Using muscle-specific dnOrai1 transgenic mice and muscle-specific Orai1 knockout mice, we demonstrated that SOCE in skeletal muscle promotes skeletal muscle growth and limits muscle fatigue.

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Mechanisms of Mitochondrial Calcium Uptake and Energy Production

Mechanisms of Mitochondrial Calcium Uptake and Energy ProductionSkeletal muscle contraction is fueled by calcium and ATP. Thus, muscle contractility is intimately linked to the proper homeostatic control of cellular levels of both calcium and ATP. In skeletal muscle, the sarcoplasmic reticulum (SR) is the primary regulator of calcium storage, release, and reuptake, while glycolysis and the mitochondria are responsible for cellular ATP production.

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Pathomechanisms of Skeletal and Cardiac Muscle Dysfunction in Myotonic Dystrophy Type I

Pathomechanisms of Skeletal and Cardiac Muscle Dysfunction in Myotonic Dystrophy Type IMyotonic dystrophy type 1 (DM1) is a multi-system disease (with skeletal muscle, cardiac, neuroendocrine involvement) that is caused by expansion of a CTG repeat in the 5’ untranslated region of the DM protein kinase (DMPK) gene. In collaboration with Dr. C. Thornton, we have investigated the molecular mechanisms by which the repeat expansion causes myotonia in myotonic dystrophy type I (DM1).

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