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Answer Key to Short Answer Questions for “Overheated: A Case Study on Skeletal Muscle Physiology” 1. David’s body temperature rises above normal during the surgery (hyperthermia). How does skeletal muscle tissue contribute to body temperature? Skeletal muscle produces heat when it contracts, which is an essential function in maintaining normal core body temperature. 2. During malignant hyperthermia, there is an increased amount of calcium released into the sarcoplasm of skeletal muscle cells. a. What organelle stores calcium in muscles cells? Sarcoplasmic reticulum b. Describe the events that must occur in the muscle cell before calcium is released from this organelle. The junctional fold of the motor end plate must be depolarized and a wave of depolarization travels along the sarcolemma. The transverse tubules carry the depolarizing current to the interior of the muscle cell where they activate voltage-sensitive channels to change shape. This shape change opens calcium-release channels in the terminal cisterns of the sarcoplasmic reticulum. Once open a massive amount of calcium floods into the sarcoplasm. 3. Jaw muscle contraction (masseter spasm) is one of the key physical findings seen in David’s case of malignant hyperthermia. Explain how calcium functions to cause contraction of a skeletal muscle cell. Calcium binding to troponin triggers it to change shape and pivot. This action pulls tropomyosin off the actin binding sites for myosin on the thin myofilament. This sets the stage for cross bridge formation. At this point, the myosin heads have already been activated by the hydrolysis of ATP before cross bridges can form. 4. Dr. Hodges notes that David’s exhaled carbon dioxide levels are elevated. List all the metabolic pathways that function to synthesize ATP for skeletal muscle contraction. Which of these pathways produces carbon dioxide as a by-product? Direct phosphorylation of ADP by creatine phosphate Anaerobic metabolism Aerobic metabolism: has the highest yield of ATP (32) and produces CO2. 5. Malignant hyperthermia causes a hypermetabolic state in skeletal muscle, which is triggered by high demands for ATP during uncontrolled muscle contractions. a. What is the role of ATP in cross bridge cycling? Activation of the myosin head is required for contraction and uses one ATP per cross bridge cycle. b. What is the role of ATP in generating a resting membrane potential? The Na+/K+ pump helps maintain resting membrane potential, which is a prerequisite for depolarization and action potential propagation. The pump hydrolyzes one ATP molecule in the transport of three Na+ out of the cell and two K+ into the cell. c. What is the role of ATP in maintaining calcium concentration gradients? Calcium must be actively pumped back into the terminal cisterns of the sarcoplasmic reticulum to terminate the contraction and relax the skeletal muscle. For every Ca2+ transported, one ATP molecule is hydrolyzed. 6. Dantrolene is the only drug available to treat malignant hyperthermia. It works by inhibiting calcium channels of the terminal cisterns of the sarcoplasmic reticulum. Explain how this inhibition helps to terminate skeletal muscle contraction. What effect would this have on David’s body temperature? Once the outflow of calcium stops, the active transport of calcium back into the SR "catches up," causing a net reduction in the concentration of calcium in the sarcoplasm. In the absence of calcium, troponin reverts back to its original shape. This pulls tropomyosin back over the myosin binding sites on the thin myofilament which blocks the formation of cross bridges between actin and myosin. Once the uncontrolled skeletal muscle contractions stop, David's body temperature would begin to fall back toward normal.