SGD 4:

SKELETAL MUSCLE PHYSIOLOGY

1. Review the steps involved in neuromuscular transmission. Would an isolated skeletal muscle immersed in a solution devoid of calcium ions contract upon stimulation of the nerve innervating it? Neuromuscular transmission: Neurons from the motor complex sends signal to the anterior horn -> Anterior horn cell depolarizes -> AP transmission in the axon -> voltage gated calcium channels in terminal button open up -> calcium influx -> exocytosis of the acetylcholine containing vesicles -> ACH transverses the synaptic cleft -> stimulates nicotinic receptors -> Sodium influx -> MP is less negative Excitatory Post Synaptic Potential (EPSP) or AP reaches threshold potential -> AP travels along the sarcolemma and T tubule -> T tubule will send signal to the sarcoplasmic reticulum -> calcium is released via the ryanodine channels (due to conformational change in the dihydropyridine) -> calcium binds with troponin C -> uncovering of actin active site -> Cross bridge cycling

2. A 20 year old female nursing student consults at the ER. Her serum potassium is 1.8 mEq/L (normal value: 3.5-5 mEq/L). What symptoms/ signs would she manifest in her neuromuscular systems? HYPOKALEMIA (1.8 mEq/L) s/sx: palpitations, skeletal muscle weakness, cramping, paralysis or paresthesia, constipation, nausea and vomiting, abdominal cramping, polyuria, polydypsia, psychosis, delirium, hallucinations, depression y Potassium (K+) ions are the predominant intracellular cations. K+ homeostasis depends on external balance (dietary intake [typically 100 mmol per day] versus excretion [95% via the kidney; 5% via the colon]) and internal balance (the distribution of K+ between intracellular and extracellular fluid compartments). The uneven distribution of K+ across cell membranes means that a mere 1% shift in its distribution can cause a 50% change in plasma K+ concentration. Hormonal mechanisms (involving insulin, -adrenergic agonists and aldosterone) modulate K+ distribution by promoting rapid transfer of K+ across the plasma membrane. Extrarenal K+ losses from the body are usually small, but can be marked in individuals with chronic diarrhea, severe burns or prolonged sweating. Under normal circumstances, the kidney's distal nephron secretes K+ and determines final urinary excretion. In patients with hypokalemia (plasma K+ concentration <3.5 mmol/l), after the exclusion of extrarenal causes, alterations in sodium ion delivery to the distal nephron, mineralocorticoid status, or a specific inherited or acquired defect in distal nephron function (each of which affects distal nephron K+ secretion), should be considered. Clinical management of hypokalemia should establish the underlying cause and alleviate the primary disorder.

a.) b.) c.) d.) e.)

3. Explain the principles and steps of cross bridge cycling? Resting fiber cross bridge is not attached to actin Cross bridge binds to actin Power stroke causes filaments to slide A new ATP binds to myosin head , allowing it to release from actin ATP is hydrolyzed, causing cross bridge to return to its original orientation

Muscle is a chemomechanical transducer. It has the ability to convert chemical energy, stored in the terminal phosphate group of ATP, into mechanical work. The myosin crossbridge, or myosin molecular motor, is the site for this energy conversion. Thus in addition to generating force and shortening, myosin is an enzyme that hydrolyzes ATP (i.e. ATPase). Biochemical cycle for ATP hydrolysis:

a) Hydrolysis occurs while myosin is detached. b) Hydrolysis of ATP primes myosin for attachment. c) Once attached to actin, the products of ATP hydrolysis are released and the myosin then undergoes a conformational change believed to be the force generating step or powerstroke. d) Myosin detaches from actin upon binding of ATP to complete one cycle of the actomyosin ATPase.

4. If the transverse tubules of a skeletal muscle are disconnected from the plasma membrane, will action potential trigger a contraction? Why? Transverse Tubules (invaginations of sarcolemma) facilitates conduction of action potential to the sarcoplasmic reticulum. Without the T tubules, the travel of AP will not reach the SR to enable release of calcium via the ryanodine channels. T tubules play a critical role in excitation-contraction coupling. Ttubules provide proximity between the electrically excitable cell membrane and the sarcoplasmic reticulum, the main intracellular Ca2+ store.

5. What conditions would produce maximum tension in a skeletal muscle fiber? - In a skeletal muscle fiber, the amount of tension generated during a contraction depends on the number of pivoting cross-bridges in all the sarcomeres along all the myofibrils. The number of crossbridges that can form depends on the degree of overlap between thick filaments and thin filaments. When the muscle fiber is stimulated to contract, only myosin heads in the zone of overlap can bind to active sites and produce tension. The tension produced by the entire muscle fiber can thus be related to the structure of an individual sarcomere. - Within the optimal range of sarcomere lengths, the maximum number of cross-bridges can form and the tension produced is highest.

6. Differentiate the types of muscle fibers- Type 1, 2A and 2B according to: a. Myosin isoenzyme b. Conduction velocity c. Sarcoplasmic reticulum capacity d. Source of ATP e. Fatigability f. Glycolytic capacity g. Oxidative capacity h. Diameter

Type 1 (Slow Oxidative)

Type 2A (Avian)

Type 2B

Myosin isoenzyme Conduction velocity Sarcoplasmic reticulum capacity Source of ATP Fatigability Glycolytic capacity Oxidative capacity Diameter

Slow Slow Moderate Oxidative phosphorylation no moderate high moderate

fast fast high both no high high Small

Fast Fast High glycolysis Yes High Low Large