MS Block Physiology

A 56-year-old woman with severe muscle weakness is hospitalized. The only abnormality in her laboratory values is an elevated serum K+ concentration. The elevated serum K+ causes muscle weakness because (A) the resting membrane potential is hyperpolarized (B) the K+ equilibrium potential is hyperpolarized (C) the Na+ equilibrium potential is hyperpolarized (D) K+ channels are closed by depolarization (E) K+ channels are opened by depolarization (F) Na+ channels are closed by depolarization (G) Na+ channels are opened by depolarization

F Elevated serum K+ concentration causes depolarization of the K+ equilibrium potential and therefore depolarization of the resting membrane potential in skeletal muscle. Sustained depolarization closes the inactivation gates on Na+ channels and prevents the occurrence of action potentials in the muscle.

Indicate whether each of the following is activated (Increased), inhibited (decreased), or unchanged in the operation of the Golgi tendon reflex. a) Golgi tendon organs b) 1a afferent fibers c) 1b afferent fibers d) inhibitory interneurons e) α motoneurons

Golgi tendon organs, 1b afferent fibers & inhibitor interneurons: activated 1a afferent fibers (involved in stretch reflex): unchanged α motoneurons: inhibited

Which phase of the nerve action potential is responsible for propagation of the action potential to neighboring sites?

Upstroke of the action potential

A hyperpolarizing receptor potential makes the membrane potential____negative and ____ the likelihood of action potentials occurring. a) more, increases b) more, decreases c) less, increases d) less, decreases

B

During which of the following steps in cross-bridge cycling in skeletal muscle is ATP bound to myosin? a) rigor b) conformational change in myosin that reduces its affinity for actin c) power stroke

B

How does the intracellular Na+1 concentration change following inhibition of Na+1/K+1 ATPase? a) decreases b) increases c) stays the same

B

What effect would increasing the internal resistance (Ri) of a nerve fiber have on conduction velocity? a) increase b) decrease c) no change

B

Sensory receptor potentials (A) are action potentials (B) always bring the membrane potential of a receptor cell toward threshold (C) always bring the membrane potential of a receptor cell away from threshold (D) are graded in size, depending on stimulus intensity (E) are all-or-none

D Receptor potentials are graded potentials that may bring the membrane potential of the receptor cell either toward (depolarizing) or away from (hyperpolarizing) threshold. Receptor potentials are not action potentials, although action potentials (which are all-or-none) may result if the membrane potential reaches threshold.

Which of the following classes of drugs are contraindicated in a patient with myasthenia gravis? a) nicotinic receptor antagonist b) inhibitor of choline reuptake c) acetylcholinesterase inhibitor d) inhibitor of Ach release e) A, B, D

E

When two acetylcholine molecules bind to a nicotinic receptor on skeletal muscle, the channel opens and allows transmembrane passage of ions. The resulting ion flux is dominated by which of the following choices under normal physiologic conditions? A. Ca2+ B. Mg2+ C. H+ D. Cl- E. Na+

E The nicotinic acetylcholine receptor (nAChR) is a nonspecific cation channel that allows passage of Na+, K+, and Ca2+. The Ca2+ flux is small and not physiologically significant. The electrochemical gradients for Na+ and K+ are normally configured such that the nAChR supports simultaneous Na+ influx and K+ efflux. Na+ influx dominates this exchange, however, and the myocyte depolarizes. Membrane depolarization then opens voltage-dependent Na+ channels, which allows an action potential to propagate across the sarcolemma and down the T-tubule system to initiate muscle contraction. The nAChR does not support significant H+, Cl-, or Mg2+ fluxes under normal, physiologic conditions.

What effect would increasing nerve fiber diameter have on conduction velocity? a) increase b) decrease c) no change

A

What type of precursor cells found in bone express RANKL (receptor activator of nuclear factor κB ligand) on their surface to facilitate bone resorption? A. Osteoblast B. Osteoclast C. Osteocyte D. Bone lining cell E. Hematopoietic

A Bone resorption and remodeling involves several cell types that work together within a bone remodeling compartment. Osteoblast precursors express receptor activator of nuclear factor κB (RANK) ligand (RANKL) on their surface. RANKL binds to RANK, a receptor expressed on the surface of osteoclast precursors (these are hematopoietic precursors), causing several such cells to fuse and form large multinucleated osteoclasts. Osteoclasts digest bone and release its mineral content for return to blood. Osteocytes are cells embedded in the bone matrix that monitor stress and integrity. Bone lining cells are found on the bone surface and signal a need for remodeling as needed.

A 24-year-old medical student is an avid bodybuilder who lifts weights approximately 2 to 3 hours per day. Which of the following best describes the contractile response of skeletal muscle? a. More tension is produced when the muscle contracts isometrically than isotonically. b. Muscle contraction starts after the action potential is over. c. Muscle length decreases to a greater extent in isometric than in isotonic contractions. d. Repeated stimulation decreases the magnitude of the muscle contraction. e. The duration of the action potential exceeds the duration of skeletal muscle contraction.

A In isometric (same measure or length) contractions, muscle contraction increases the tension of the muscle. Isometric contraction is possible because muscles have elastic and viscous elements in series with the contractile elements, so contraction can occur without an appreciable decrease in length. In contrast, isotonic (same tension) contractions are contractions against a constant load, which decrease muscle length. Muscle fiber membrane depolarization during an action potential initiates muscle contraction via a process called excitation-contraction coupling. The duration of the contractile response of skeletal muscle (muscle twitch) exceeds the duration of the action potential, but varies with muscle fiber type. Because the muscle contractile mechanism does not have a refractory period, repeated stimulation before relaxation causes greater tension development than during a single muscle twitch, a process called summation of contractions.

A 36-year-old woman has a parathyroid hormone (PTH)-secreting tumor. Which of the following might be expected to increase as a result of chronic PTH elevation? A. Bone resorption B. Bone deposition C. Ca2+ excretion from the intestines D. PO43- absorption from the intestines E. PO43- reabsorption from the kidneys

A Parathyroid hormone (PTH) release from parathyroid glands is normally regulated by plasma Ca2+ levels. When plasma Ca2+ (or Mg2+) levels decrease, PTH is secreted to stimulate Ca2+ resorption from bone. PTH's effects are mediated by PTH receptors on osteoblasts, which then recruit osteoclasts to a bone remodeling site. PTH does not stimulate bone deposition. PTH causes Ca2+ reabsorption (not excretion) by the renal distal tubule. PTH also inhibits PO43- reabsorption by the renal proximal tubule, thereby increasing excretion rates.

Phospholamban is a regulatory protein associated with the cardiac sarcoplasmic reticulum Ca2+ ATPase. Phospholamban phosphorylation would most likely increase the rate of which of the following events? A. Relaxation B. Ca2+ influx C. Crossbridge cycling D. Electrical conduction E. Nodal cell depolarization

A Phospholamban normally acts as a rate limiter on sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) function. Phospholamban phosphorylation reduces its inhibitory effects, allowing the pump to speed up. SERCA normally helps remove Ca2 from the sarcoplasm following excitation. Increasing pump speed causes sarcoplasmic free Ca2+ levels to fall faster than normal, promoting decreased relaxation times. Ca2+ influx occurs during excitation and probably would not be appreciably affected by changes in SERCA. Crossbridge cycling rate is dependent on actin-myosin interactions. Electrical conduction between myocytes is dependent on gap junction function. Although faster relaxation times do facilitate heart rate increases, the rate of nodal cell depolarization is controlled through ion channel modulation.

A distracted cook picks up and immediately drops a metal spatula that had become painfully hot to the touch. Which of the following statements best describes such reflexes? A. They are mediated by local spinal circuits. B. Pain stimuli are transduced by Ruffini endings. C. Pain stimuli are transmitted via α-motoneurons. D. They would be unaffected by demyelination. E. They are mediated by central pattern generators.

A Reflexive movements triggered by painful stimuli are mediated by spinal reflex circuits (or "arcs"). Painful stimuli are mediated by pain receptors and transmitted via myelinated sensory afferent fibers to the spinal cord. The short signal path and fibers adapted for high conduction velocity decrease reaction time. The motoneurons are also myelinated, which makes both arms susceptible to demyelinating disease. Ruffini endings sense mechanical stimulation of the skin, whereas central pattern generators are involved in establishing rhythmic movements.

A newly developed local anesthetic blocks Na+ channels in nerves. Which of the following effects on the action potential would it be expected to produce? (A) Decrease the rate of rise of the upstroke of the action potential (B) Shorten the absolute refractory period (C) Abolish the hyperpolarizing after potential (D) Increase the Na+ equilibrium potential (E) Decrease the Na+ equilibrium potential

A Blockade of the Na+ channels would prevent action potentials. The upstroke of the action potential depends on the entry of Na+ into the cell through these channels and therefore would also be reduced or abolished. The absolute refractory period would be lengthened because it is based on the availability of the Na+ channels. The hyperpolarizing afterpotential is related to increased K+ permeability. The Na+ equilibrium potential is calculated from the Nernst equation and is the theoretical potential at electrochemical equilibrium (and does not depend on whether the Na+ channels are open or closed).

Which of the following is a property of C fibers? (A) Have the slowest conduction velocity of any nerve fiber type (B) Have the largest diameter of any nerve fiber type (C) Are afferent nerves from muscle spindles (D) Are afferent nerves from Golgi tendon organs (E) Are preganglionic autonomic fibers

A C fibers (slow pain) are the smallest nerve fibers and therefore have the slowest conduction velocity.

In skeletal muscle, which of the following events occurs before depolarization of the T tubules in the mechanism of excitation-contraction coupling? (A) Depolarization of the sarcolemmal membrane (B) Opening of Ca2+ release channels on the sarcoplasmic reticulum (SR) (C) Uptake of Ca2+ into the SR by Ca2+-adenosine triphosphatase (ATPase) (D) Binding of Ca2+ to troponin C (E) Binding of actin and myosin

A In the mechanism of excitation-contraction coupling, excitation always precedes contraction. Excitation refers to the electrical activation of the muscle cell, which begins with an action potential (depolarization) in the sarcolemmal membrane that spreads to the T tubules. Depolarization of the T tubules then leads to the release of Ca2+ from the nearby sarcoplasmic reticulum (SR), followed by an increase in intracellular Ca2+ concentration, binding of Ca2+ to troponin C, and then contraction.

Which reflex is responsible for monosynaptic excitation of ipsilateral homonymous muscle? (A) Stretch reflex (myotatic) (B) Golgi tendon reflex (inverse myotatic) (C) Flexor withdrawal reflex (D) Subliminal occlusion reflex

A The stretch reflex is the monosynaptic response to stretching of a muscle. The reflex produces contraction and then shortening of the muscle that was originally stretched (homonymous muscle).

A 22-year-old woman receives botulinum toxin type A (a cholinergic presynaptic release inhibitor) injections to treat palmar hyperhidrosis (excess sweating). Her grasp is weakened by the treatments, through a decrease in the synaptic levels of what substance? A. Acetylcholinesterase B. Acetylcholine C. Calsequestrin D. Myoglobin E. Nicotinic receptors

B Botulinum toxin is a protease that prevents exocytosis and release of neurotransmitters from nerve terminals. Botulinum toxin type A is commonly used clinically to inhibit acetylcholine (ACh) release at the neuromuscular junction, which reduces synaptic ACh levels. It reduces eccrine sweat gland activity through a similar mechanism. Acetylcholinesterase, which normally degrades Ach and terminates neuromuscular signaling, would not be affected by the toxin. Myoglobin is a sarcoplasmic O2 storage and transport molecule, whereas calsequestrin is a Ca2+-binding protein found in the sarcoplasmic reticulum. Neither is directly involved neuromuscular transmission.

In a controlled experiment, radiolabeled ATP is injected into an isolated muscle. The muscle is stimulated and allowed to contract for 10 seconds. An autoradiogram from a biopsy of the muscle will show radiolabeled ATP bound to A. actin B. myosin C. sarcoplasmic reticulum D. tropomyosin E. troponin C

B During the contraction cycle, ATP binds to myosin cross-bridge heads, causing the dissociation of myosin from actin. Actin forms cross-bridges with myosin but does not bind to ATP. The sarcoplasmic reticulum is involved in storing and releasing Ca2+ for muscle contraction. Tropomyosin is a tin filament that runs alongside actin. In the absence of calcium, tropomyosin lies in the groove of the actin filament and blocks actin's myosin-binding sites. Troponin C is the calcium-binding subunit of the troponin complex. When troponin C binds calcium, a conformational change causes tropomyosin to shift, thereby exposing the myosin-binding sites on actin.

A 56-year-old woman presents with a flat red rash on the face and upper trunk and an erythematous rash on the knuckles and in the shape of a V on the neck and anterior chest. She also complains of muscle weakness with difficulty getting out of a chair and combing her hair. Laboratory findings include increased creatine phosphokinase, positive antinuclear antibody, and anti-Mi2 dermatomyositis-specific antibodies. In addition to oral prednisone, physical therapy is ordered with the goal of improving muscle strength, and thus ability to perform activities of daily living. How does repetitive stimulation of a skeletal muscle fiber cause an increase in contractile strength? a. By increasing the concentration of calcium in the myoplasm b. By increasing the duration of cross-bridge cycling c. By increasing the magnitude of the end-plate potential d. By increasing the number of muscle myofibrils generating tension e. By increasing the velocity of muscle contraction

B Each time a skeletal muscle fiber is stimulated by an α-motoneuron, enough Ca2+ is released from its SR to fully activate all the troponin within the muscle. Therefore, every cross bridge can contribute to the generation of tension. However, the transmission of force from the cross bridges to the tendon does not occur until the series elastic component (SEC) of the muscle is stretched. Repetitive firing increases the amount of SEC stretch by maintaining cross-bridge cycling for a longer period of time. Repetitive firing increases neither the concentration of Ca2+ within the myoplasm, the number of myofibrils that are activated, nor the magnitude of the end-plate potential. Because all of the cross bridges are activated each time a skeletal muscle fiber is activated, an increase in Ca2+ concentration would have no effect on muscle strength. The skin findings, along with limitation in rising from a seated position or combing hair, are suggestive of proximal muscle weakness, characteristic of dermatomyositis.

What are the mineral crystals that resist compression and give bones their characteristic strength and resilience? A. Urate B. Hydroxyapatite C. Glycosaminoglycan D. Creatinine E. Calcium oxalate

B Hydroxyapatite is a crystalline mineral containing calcium and phosphate. Hydroxyapatite crystals are cemented within collagen fibers and then bundles of mineralized fibers embedded in ground substance to create a material that has a high resistance to compression and tensile stress. Urate, creatinine, and calcium oxalate are found at high concentrations in urine. When sufficiently concentrated, they form crystals that may be observed in urine sediments. Glycosaminoglycan is a mucopolysaccharide found in ground substance, which fills the spaces between all cells, including bone.

A 35-year-old woman presents at her ophthalmologist's office with a chief complaint of bilateral drooping eyelids. A complete history reveals that the woman has also been experiencing generalized fatigue and weakness that only improves if she takes frequent naps. The ophthalmologist suspects a synaptogenic basis for the ptosis and refers her to a neurologist. The patient is found to have circulating antibodies to nicotinic acetylcholine receptors on the motor endplate. A drug is administered that increases the force of muscle contraction but causes bradycardia in the patient. What is the most likely mechanism of action of the drug? a. Decreases the concentration of calcium in the extracellular fluid b. Decreases the metabolic breakdown of acetylcholine c. Increases α-motoneuron discharge rate d. Increases the affinity of the skeletal muscle acetylcholine receptors to acetylcholine e. Increases the amount of acetylcholine released by α-motoneurons

B Myasthenia gravis is an autoimmune disorder of neuromuscular transmission. The major clinical features are fluctuating fatigue and weakness that improve after a period of rest and after administration of acetylcholinesterase inhibitors. Muscles with small motor units, such as ocular muscles, are most often affected. In severe cases, all muscles are weak, including the diaphragm and intercostal muscles, and death may result from respiratory failure. In 90% of patients, circulating antibodies to the nicotinic acetylcholine receptors on the motor end plate are present. The antibodies block acetylcholine binding and receptor activation.

A 5-year-old boy presents with abnormal running, jumping, and hopping. His parents have observed that he uses his arms to climb up his legs when rising from the floor. The pediatrician suspects Duchenne muscular dystrophy, and electromyography confirms a myopathy. The amount of force produced by a skeletal muscle can be increased by which of the following? a. Decreasing extracellular Ca2+ b. Decreasing the interval between contractions c. Increasing the activity of acetylcholine esterase d. Increasing extracellular Mg2+ e. Increasing the preload beyond 2.2 mm

B When the interval between skeletal muscle contractions is small, the force produced by the two successive contractions will summate. The shorter the interval between the contractions, the greater the summation will be. Maximum summation is called tetanus. Decreasing extracellular Ca2+ will increase the excitability of skeletal muscle fibers but does not have a direct effect on contractile force. Increasing the Mg2+ concentration will decrease skeletal muscle excitability. Increasing the preload beyond 2.2 mm decreases the overlap between thick and thin filaments, and therefore decreases the force of contraction. Increasing the activity of acetylcholine esterase enhances the hydrolysis of ACh, and therefore decreases the likelihood that muscle contraction will be initiated.

Cardiac muscle contraction is dependent on a rise in sarcoplasmic Ca2+ concentration. The bulk of the Ca2+ required for full force generation flows through which of the following Ca2+ channel types? A. Dihydropyridine receptors B. Ryanodine receptors C. Inositol trisphosphate-gated channels D. Transient receptor-potential channels E. Stretch-activated channels

B Full force development by a cardiac myocyte relies on Ca2+ release from stores in the sarcoplasmic reticulum (SR). Release is mediated by Ca2+-induced Ca2+ release (CICR) channels, also known as ryanodine receptors. Dihydropyridine receptors are L-type Ca2+ channels that mediate voltage-gated Ca2+ fluxes across the T-tubule membrane. Ca2+ influx via this pathway acts as a trigger for CICR. Inositol trisphosphate mediates Ca2+ release from the SR in smooth muscle. Transient receptor-potential channels are found in many tissues, often mediating cellular sensory stimulus transduction. Stretch-activated channels are also widespread but ryanodine receptors are the principal pathway for Ca2+ fluxes during contraction.

Which of the following temporal sequences is correct for excitation-contraction coupling in skeletal muscle? (A) Increased intracellular [Ca2+]; action potential in the muscle membrane; cross-bridge formation (B) Action potential in the muscle membrane; depolarization of the T tubules; release of Ca2+ from the sarcoplasmic reticulum (SR) (C) Action potential in the muscle membrane; splitting of adenosine triphosphate (ATP); binding of Ca2+ to troponin C (D) Release of Ca2+ from the SR; depolarization of the T tubules; binding of Ca2+ to troponin C

B The correct sequence is action potential in the muscle membrane; depolarization of the T tubules; release of Ca2+ from the sarcoplasmic reticulum (SR); binding of Ca2+ to troponin C; cross-bridge formation; and splitting of adenosine triphosphate (ATP).

The correct temporal sequence for events at the neuromuscular junction is (A) action potential in the motor nerve; depolarization of the muscle end plate; uptake of Ca2+ into the presynaptic nerve terminal (B) uptake of Ca2+ into the presynaptic terminal; release of acetylcholine (ACh); depolarization of the muscle end plate (C) release of ACh; action potential in the motor nerve; action potential in the muscle (D) uptake of Ca2+ into the motor end plate; action potential in the motor end plate; action potential in the muscle (E) release of ACh; action potential in the muscle

B Acetylcholine (ACh) is stored in vesicles and is released when an action potential in the motor nerve opens Ca2+ channels in the presynaptic terminal. Ach diffuses across the synaptic cleft and opens Na+ and K+ channels in the muscle end plate, depolarizing it (but not producing an action potential). Depolarization of the muscle end plate causes local currents in adjacent muscle membrane, depolarizing the membrane to threshold and producing action potentials.

A 42-year-old man with myasthenia gravis notes increased muscle strength when he is treated with an acetylcholinesterase (AChE) inhibitor. The basis for his improvement is increased (A) amount of acetylcholine (ACh) released from motor nerves (B) levels of ACh at the muscle end plates (C) number of ACh receptors on the muscle end plates (D) amount of norepinephrine released from motor nerves (E) synthesis of norepinephrine in motor nerves

B Myasthenia gravis is characterized by a decreased density of acetylcholine (ACh) receptors at the muscle end plate. An acetylcholinesterase (AChE) inhibitor blocks degradation of ACh in the neuromuscular junction, so levels at the muscle end plate remain high, partially compensating for the deficiency of receptors.

Which of the following is a characteristic of nuclear bag fibers? (A) They are one type of extrafusal muscle fiber (B) They detect dynamic changes in muscle length (C) They give rise to group Ib afferents (D) They are innervated by α-motoneurons

B Nuclear bag fibers are one type of intrafusal muscle fiber that make up muscle spindles. They detect dynamic changes in muscle length, give rise to group Ia afferent fibers, and are innervated by γ-motoneurons. The other type of intrafusal fiber, the nuclear chain fiber, detects static changes in muscle length.

An 8-year-old girl experiences two to three episodes of proximal muscle weakness a day. The attacks are precipitated by rest following exercise and last 1 to 2 hours. Serum potassium concentration during the attack of weakness is normal. Which of the following is most likely to cause the muscle weakness in periodic hyperkalemic paralysis? a. Decreased potassium conductance in muscle cells b. Hyperpolarization of muscle cells c. Inactivation of sodium channels in muscle cells d. Increased duration of action potentials produced by α-motoneurons e. Increased release of neurotransmitters from α-motoneurons

C Periodic hyperkalemic paralysis is a disorder of muscle membrane excitability resulting from a sodium channel disorder. Inactivation of the sodium channels on the skeletal muscle membrane prevents action potentials from being produced, and therefore leads to muscle weakness or paralysis. Although the exact mechanism of periodic hyperkalemic paralysis is not known, it appears to be due to a mutation in the gene coding for the sodium inactivation gate.

A 35-year-old woman having an anxiety attack collapses. The emergency medical technician who arrives on the scene notes that she is hyperventilating and has facial and carpopedal spasms. What causes increased excitability of nerves and muscle membranes that can lead to continuous contraction of skeletal muscle fibers? a. Activation of sodium channels at more negative membrane potentials b. Decreased release of inhibitory neurotransmitter from nerve terminals c. Depolarization of the nerve and muscle membranes d. Increased magnitude of the action potentials invading nerve terminals e. Spontaneous release of calcium from the sarcoplasmic reticulum (SR)

C Membrane excitability is related to the ease with which depolarization opens Na+ channels. The opening of the Na+ channel in response to depolarization is, in part, related to the extracellular Ca2+ concentration; the lower the extracellular Ca2+ concentration, the easier it is for Na+ channels to open when the membrane depolarizes. Hyperventilation (lowering arterial CO2 tension) decreases extracellular Ca2+ concentration by increasing arterial pH. When pH rises, H+ is released from plasma proteins in exchange for Ca2+, and ionized Ca2+ concentration decreases.

A 26-year-old medical student walks briskly down the hallway to grand rounds while eating a hamburger and fries on the way. What is the major difference in the contractile responses occurring in his smooth versus skeletal muscles? a. The mechanism of force generation b. The nature of the contractile proteins c. The role of calcium in initiating contraction d. The source of activator calcium e. The source of energy used during contraction

C The greatest difference in excitation-contraction coupling between skeletal muscle and smooth muscle involves the role of calcium in initiating contraction. In smooth muscle, calcium binds to and activates calmodulin, which, by activating myosin light chain kinase, catalyzes the phosphorylation of the 20,000-Da myosin light chain. Once the light chains are phosphorylated, myosin cross bridges bind to actin on the thin filaments, which initiates contraction. In skeletal muscle, calcium binds to troponin, which removes the tropomyosin-mediated inhibition of the actin-myosin interactions. Once the inhibition is removed, cross-bridge cycling (and contraction) begins. In both smooth and skeletal muscles, the cycling of cross bridges generates force. ATP provides the energy for the cycling of the cross bridges in both muscles. In skeletal muscle, activator calcium comes exclusively from the SR, whereas in smooth muscle calcium can come from both the SR and the extracellular fluid.

In skeletal muscle at muscle lengths less than the length that generates maximum active tension is active tension...? a) greater than total tension b) less than total tension c) approximately equal to total tension

C passive tension is negligible in this range

Which characteristic or component is shared by skeletal muscle and smooth muscle? (A) Thick and thin filaments arranged in sarcomeres (B) Troponin (C) Elevation of intracellular [Ca2+] for excitation-contraction coupling (D) Spontaneous depolarization of the membrane potential (E) High degree of electrical coupling between cells

C An elevation of intracellular [Ca2+] is common to the mechanism of excitation-contraction coupling in skeletal and smooth muscle. In skeletal muscle, Ca2+ binds to troponin C, initiating the cross-bridge cycle. In smooth muscle, Ca2+ binds to calmodulin. The Ca2+-calmodulin complex activates myosin light chain kinase, which phosphorylates myosin so that shortening can occur. The striated appearance of the sarcomeres and the presence of troponin are characteristic of skeletal, not smooth, muscle. Spontaneous depolarizations and gap junctions are characteristics of unitary smooth muscle but not skeletal muscle.

Which reflex is responsible for polysynaptic excitation of contralateral extensors? (A) Stretch reflex (myotatic) (B) Golgi tendon reflex (inverse myotatic) (C) Flexor withdrawal reflex (D) Subliminal occlusion reflex

C Flexor withdrawal is a polysynaptic reflex that is used when a person touches a hot stove or steps on a tack. On the ipsilateral side of the painful stimulus, there is flexion (withdrawal); on the contralateral side, there is extension to maintain balance.

Muscle stretch leads to a direct increase in firing rate of which type of nerve? (A) α-Motoneurons (B) γ-Motoneurons (C) Group Ia fibers (D) Group Ib fibers

C Group Ia afferent fibers innervate intrafusal fibers of the muscle spindle. When the intrafusal fibers are stretched, the group Ia fibers fire and activate the stretch reflex, which causes the muscle to return to its resting length.

Which of the following would occur as a result of the inhibition of Na+, K+-ATPase? (A) Decreased intracellular Na+ concentration (B) Increased intracellular K+ concentration (C) Increased intracellular Ca2+ concentration (D) Increased Na+-glucose cotransport (E) Increased Na+-Ca2+ exchange

C Inhibition of Na+, K+-adenosine triphosphatase (ATPase) leads to an increase in intracellular Na+ concentration. Increased intracellular Na+ concentration decreases the Na+ gradient across the cell membrane, thereby inhibiting Na+-Ca2+ exchange and causing an increase in intracellular Ca2+ concentration. Increased intracellular Na+ concentration also inhibits Na+-glucose cotransport.

A 32-year-old woman undergoing an appendectomy develops malignant hyperthermia following halothane anesthesia. What changes in skeletal muscle cause body temperature to increase in this condition? a. An increase in the refractory period of the α-motoneurons b. Inability of skeletal muscle cells to repolarize c. Excess calcium release from the SR during muscle contraction d. Production of endogenous muscle pyrogens e. Rapid repetitive firing of the presynaptic terminals of α-motoneurons

C Malignant hyperthermia is a life-threatening increase in metabolic rate and body temperature attributed to a mutation of the ryanodine receptor in skeletal muscle. The ryanodine receptor, or calcium release channel on the SR is normally opened when skeletal muscle is activated. The flow of calcium through the open ryanodine receptor binds to troponin and initiates muscle contraction. The metabolic activity accompanying muscle contraction can warm the body. If a mutation in the ryanodine receptor causes uncontrolled release of calcium from the SR, the body temperature can rise to levels that cause brain damage.

A 28-year-old man qualifies to run the Boston marathon. He undertakes an endurance training regimen designed to improve marathon performance. Which of the following properties is greater in Type I compared to Type IIb/x skeletal muscle fibers, thereby promoting distance running success? a. Diameter of the muscle fibers b. Force of contraction c. Glycolytic capacity d. Oxidative capacity e. Speed of contraction

D Skeletal muscle is a heterogeneous tissue made up of three different fiber types—Type I (slow twitch, slow oxidative, red), Type IIa (intermediate, fast-twitch, fast oxidative glycolytic, white), and Type IIb/x (fast-twitch, fast glycolytic, white). Other properties of Type I compared with Type II fiber types are smaller diameter, less fatigability, decreased force of contraction, and decreased speed of contraction.

The velocity of conduction of action potentials along a nerve will be increased by (A) stimulating the Na+-K+ pump (B) inhibiting the Na+-K+ pump (C) decreasing the diameter of the nerve (D) myelinating the nerve (E) lengthening the nerve fiber

D Myelin insulates the nerve, thereby increasing conduction velocity; action potentials can be generated only at the nodes of Ranvier, where there are breaks in the insulation. Activity of the Na+-K+ pump does not directly affect the formation or conduction of action potentials. Decreasing nerve diameter would increase internal resistance and, therefore, slow the conduction velocity.

A 42-year-old jackhammer operator presents with decreased high-frequency vibration sensitivity in the glabrous skin of the hands. Which receptor is most likely being affected? A. Ruffini endings B. Merkel disks C. Free nerve endings D. Pacini corpuscles E. Hair sensory fibers

D Pacini corpuscles are rapidly adapting tactile receptors responsible for sensing vibrations in the 40-500 Hz range. Glabrous skin does not have hair and, therefore, no hair sensory fibers. Ruffini endings are slowly adapting tactile receptors that sense skin stretch rather than vibrations. Merkel disks sense light skin pressure. Glabrous skin also contains free nerve endings, but these are less sensitive to vibration than are Pacini corpuscles.

An 83-year-old man with myasthenia gravis is unable to eat foods such as steak because of bulbar muscle fatigue. Studies of the man's bulbar muscles during contraction might have revealed which of the following compared with normal? A. Decreased α -motoneuron activity B. Decreased γ-motoneuron activity C. Decreased Ia sensory afferent activity D. Decreased Ib sensory afferent activity E. Decreased II sensory afferent activity

D The antibodies that are produced in patients with myasthenia gravis destroy the nicotinic acetylcholine receptor, interfering with normal excitation and force development. Muscle tension development during contraction is sensed by Golgi tendon organs, which signal via group Ib sensory afferents. Contraction is initiated by α-motoneurons, which might be expected to signal normally, as would the γ-motoneurons that initiate intrafusal fiber contraction. Group Ia and group II afferents relay sensory information from muscle spindles when a muscle is stretched.

Which of the following cytoskeletal proteins functions like a spring, limiting the extent to which the sarcomere can be stretched? A. α-Actinin B. Dystrophin C. Nebulin D. Titin E. Z disk

D Titin is a massive, thick filament-associated structural protein that limits sarcomere length when a muscle is stretched. Thin filament-associated proteins do not act as springs but, rather, provide structural integrity. For example,α-actinin binds the ends of thin filaments to Z disks (structural plates that serve as attachment points for thin filaments); dystrophin anchors the contractile array within the cytoskeletal framework; and nebulin, which extends the length of the actin filament, is believed to establish thin-filament length.

An 18-month-old boy presents with delayed dentation, short stature, difficulty and painful walking, and bowing of the legs. The history reveals that he has been breast-fed, but that he has not been receiving daily vitamin D supplementation. A defect in which of the following can explain his findings? a. Blood supply to the haversian canals b. Bone formation by osteoblasts c. Bone resorption by osteoclasts d. Calcification of the bone matrix e. Composition of bone collagen

D Vitamin D deficiency causes defective calcification of the bone matrix as a result of inadequate delivery of Ca2+ and PO43− to the sites of mineralization. The disease in children is called rickets and is characterized by growth retardation, weakness and bowing of the weight-bearing bones, dental defects, and hypocalcemia, which increases parathyroid hormone and urinary phosphate losses. Although breast feeding is the preferred nutritional source for infants, breast-fed infants require daily vitamin D supplementation. In addition to dietary vitamin D deficiency, several different types of inheritance lead to the vitamin D deficiency disorders, including X-linked dominant and autosomal dominant hypophosphatemic rickets, vitamin D-dependent rickets Type I, an autosomal recessive disorder caused by inactivating mutations in the gene encoding 1α-hydroxylase enzyme, and vitamin D-dependent rickets Type II, in which there is end-organ resistance to 1,25(OH)2D3, which is also usually inherited as an autosomal recessive disorder.

An inhibitory postsynaptic potential (A) depolarizes the postsynaptic membrane by opening Na+ channels (B) depolarizes the postsynaptic membrane by opening K+ channels (C) hyperpolarizes the postsynaptic membrane by opening Ca2+ channels (D) hyperpolarizes the postsynaptic membrane by opening Cl− channels

D An inhibitory postsynaptic potential hyperpolarizes the postsynaptic membrane, taking it farther from threshold. Opening Cl− channels would hyperpolarize the postsynaptic membrane by driving the membrane potential toward the Cl− equilibrium potential (about −90 mV). Opening Ca2+ channels would depolarize the postsynaptic membrane by driving it toward the Ca2+ equilibrium potential.

During the upstroke of the nerve action potential (A) there is net outward current and the cell interior becomes more negative (B) there is net outward current and the cell interior becomes less negative (C) there is net inward current and the cell interior becomes more negative (D) there is net inward current and the cell interior becomes less negative

D During the upstroke of the action potential, the cell depolarizes or becomes less negative. The depolarization is caused by inward current, which is, by definition, the movement of positive charge into the cell. In nerve and in most types of muscle, this inward current is carried by Na+

Autoimmune diseases such as multiple sclerosis cause neurological impairment by affecting axon conduction velocity. Which of the following would slow axonal signal propagation to the greatest extent? A. Increasing axon diameter B. Increasing axon length C. Increasing myelin thickness D. Decreasing leak-channel density E. Decreasing depolarization rate

E Axonal conduction velocity is dependent on the rate of membrane depolarization during an action potential, which, in turn, is a function of channel gating kinetics. Conduction velocity would also be reduced by decreasing (not increasing) axon diameter or by demyelination, which would increase current loss via leak channels. Increasing leak-channel density might also be expected to slow axonal conduction velocity. Conduction velocity is independent of axonal length.

A 24-year-old medical student is an avid bodybuilder who lifts weights approximately 2 to 3 hours per day. Which of the following best describes the action potential of skeletal muscle during his workout? a. It causes the immediate uptake of Ca2+ into the lateral sacs of the SR. b. It has a prolonged plateau phase. c. It is longer than the action potential of cardiac muscle. d. It is not essential for muscle contraction. e. It spreads inward to all parts of the muscle via the T-tubules.

E Depolarization of the muscle fiber is essential for initiating muscle contraction. The action potential of skeletal muscle is transmitted to all of the fibrils along T-tubules, triggering the release (not uptake) of Ca2+ from the lateral sacs of the SR next to the T-system. The electrical events in skeletal muscle and the ionic fluxes underlying them are similar to those in nerve. In contrast, the action potential in cardiac muscle is longer and has a prolonged plateau phase.

A 62-year-old man presents with a hypokinetic movement disorder characterized by paucity and slowness of voluntary movement (bradykinesia). Which of the following characterizes the order of recruitment during normal voluntary movement? a. Anaerobic fibers are recruited before aerobic fibers b. Fast muscle fibers are recruited before slow muscle fibers c. Large muscle fibers are recruited before small muscle fibers d. Poorly perfused muscle fibers are recruited before richly perfused muscle fibers e. Weak muscle fibers are recruited before strong muscle fibers

E During most normal reflex or voluntary movements, small spinal moto-neurons are recruited before large motoneurons. In general, small, weak, slow, fatigue-resistant muscle fibers are innervated by small spinal moto-neurons, whereas large spinal motoneurons innervate large, fast, strong, easily fatigable muscle fibers. The slow fatigue-resistant muscle fibers have a dense capillary network for perfusion and use mitochondrial oxidative metabolism to produce adenosine triphosphate (ATP).

A 26-year-old male golfer presents with a chief complaint of muscle stiffness, pain, and cramping that occurs when walking uphill, and is worse when he is carrying his golf bag. He has had these symptoms for a while, but attributed them to just being out of shape until he noticed that his urine was burgundy colored following intense exercise. The differential diagnosis includes McArdle disease, which results from a deficiency of which of the following enzymes? a. Debranching enzyme b. Galactose 1-phosphate uridyl transferase c. Glucose-6-phosphatase d. Glycogen synthase e. Myophosphorylase

E In McArdle disease, glycogen accumulates in skeletal muscles because of a deficiency of myophosphorylase (muscle glycogen phosphorylase). Without adequate myophosphorylase, patients cannot break down their muscle glycogen to provide the energy for muscle contraction, except during normal activity or mild exercise. Thus, they have a greatly reduced exercise tolerance. McArdle (type V glycogenosis) is 1 of the 12 types of glycogen storage diseases, all resulting in abnormal glycogen metabolism and an abnormal accumulation of glycogen within cells. Type V glycogen storage disease is an autosomal recessive disorder. It is by far the most common of the glycolytic defects associated with exercise intolerance. The burgundy-colored urine results from myoglobinuria secondary to rhabdomyolysis.

What type of smooth muscle Ca2+ channels localize to plasma membrane caveolae and are gated primarily by membrane potential change? A. Ca2+-induced Ca2+ release channels B. Receptor-operated Ca2+ channels C. Store-operated Ca2+ channels D. Inositol trisphosphate-gated Ca2+ channels. E. L-type Ca2+ channels

E L-type Ca2+ channels are voltage gated, opening in response to membrane depolarization. They are found in many cell types, including smooth muscle, where they are concentrated within plasma membrane pockets called caveolae. Receptor-operated Ca2+ channels open when a ligand binds to the associated receptor, rather than a voltage change. Ca2+-induced Ca2+ release channels and inositol trisphosphate-gated Ca2+ channels are located on the sarcoplasmic reticulum membrane and mediate Ca2+ store release. Store-operated Ca2+ channels are used to top off intracellular Ca2+ stores with extracellular Ca2+ during muscle relaxation. Channel opening is controlled by a store Ca2+ sensor (Stim1).

Which of the following reflexes comprises only one synapse? a) knee-jerk reflex b) Golgi tendon reflex c) stretch reflex d) the reflex involved when one removes a hand from a hot stove e) A & C

E knee-jerk reflex is an example of a stretch reflex

Adenosine triphosphate (ATP) is used indirectly for which of the following processes? (A) Accumulation of Ca2+ by the sarcoplasmic reticulum (SR) (B) Transport of Na+ from intracellular to extracellular fluid (C) Transport of K+ from extracellular to intracellular fluid (D) Transport of H+ from parietal cells into the lumen of the stomach (E) Absorption of glucose by intestinal epithelial cells

E All of the processes listed are examples of primary active transport (and therefore use adenosine triphosphate [ATP] directly), except for absorption of glucose by intestinal epithelial cells, which occurs by secondary active transport (i.e., cotransport). Secondary active transport uses the Na+ gradient as an energy source and, therefore, uses ATP indirectly (to maintain the Na+ gradient).

29. Which of the following causes rigor in skeletal muscle? (A) Lack of action potentials in motoneurons (B) An increase in intracellular Ca2+ level (C) A decrease in intracellular Ca2+ level (D) An increase in adenosine triphosphate (ATP) level (E) A decrease in ATP level

E Rigor is a state of permanent contraction that occurs in skeletal muscle when adenosine triphosphate (ATP) levels are depleted. With no ATP bound, myosin remains attached to actin and the cross-bridge cycle cannot continue. If there were no action potentials in motoneurons, the muscle fibers they innervate would not contract at all, since action potentials are required for release of Ca2+ from the sarcoplasmic reticulum (SR). When intracellular Ca2+ concentration increases, Ca2+ binds troponin C, permitting the cross-bridge cycle to occur. Decreases in intracellular Ca2+ concentration cause relaxation.

During a nerve action potential, a stimulus is delivered as indicated by the arrow shown in the following figure. In response to the stimulus, a second action potential stimulus (A) of smaller magnitude will occur (B) of normal magnitude will occur (C) of normal magnitude will occur but will be delayed (D) will occur but will not have an overshoot (E) will not occur

E Because the stimulus was delivered during the absolute refractory period, no action potential occurs. The inactivation gates of the Na+ channel were closed by depolarization and remain closed until the membrane is repolarized. As long as the inactivation gates are closed, the Na+ channels cannot be opened to allow for another action potential.

Repeated stimulation of a skeletal muscle fiber causes a sustained contraction (tetanus). Accumulation of which solute in intracellular fluid is responsible for the tetanus? (A) Na+ (B) K+ (C) Cl− (D) Mg2+ (E) Ca2+ (F) Troponin (G) Calmodulin (H) Adenosine triphosphate (ATP)

E During repeated stimulation of a muscle fiber, Ca2+ is released from the sarcoplasmic reticulum (SR) more quickly than it can be reaccumulated; therefore, the intracellular [Ca2+] does not return to resting levels as it would after a single twitch. The increased [Ca2+] allows more cross-bridges to form and, therefore, produces increased tension (tetanus). Intracellular Na+ and K+ concentrations do not change during the action potential. Very few Na+ or K+ ions move into or out of the muscle cell, so bulk concentrations are unaffected. Adenosine triphosphate (ATP) levels would, if anything, decrease during tetanus.