8. A 100 kg subject was injected with 2 ml of a solution containing 30 mg/ml of an inert substance. After equilibration, the plasma concentration of

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1 Unit 1 MEDICAL PHYSIOLOGY: SECTION I (CELLULAR PHYSIOLOGY) Part 1 Body Fluid Spaces Dr. Robert Banks Department of Molecular and Cellular Physiology 1. 5 ml of a solution containing 2 mg/ml Evans Blue dye and 2 mg/ml inulin were injected into a 100 kg individual. Assuming no loss of either substance, which of the following pairs of plasma concentration would you expect after a steady state was reached. EVANS BLUE INULIN A. 2 microg/ml 100 microg/ml B. 2 microg/ml 0.5 microg/ml C. 2 microg/ml 15 microg/ml D. 0.2 microg/ml 100 microg/m E. 5 microg/ml 1.5 microg/ml 2. In a normal 70 kg individual the A. amount of Na (atomic wt. 23) in the extracellular fluid space (ECF) is about 45 gm. B. ECF is approximately 10% of the body weight. C. ratio of the plasma volume to the whole blood volume is 0.4. D. ECF K + concentration is 10 meq/1. E. plasma Cl concentration is 140 meq/1. 3. Which one of the following would result in a decrease in intracellular fluid volume? A. an infusion of a solution of 0.9 gm% NaCl. B. an infusion of a solution of 0.9 gm% urea. C. a decrease in arterial blood pressure. D. a decrease in albumin synthesis by the liver. E. sweating. 4. Which of the following statements concerning the interstitial fluid is correct? A. its volume could be measured with a combination of Evans Blue and heavy water. B. its volume increases as the colloid osmotic pressure of plasma decreases. C. it is not in osmotic equilibrium with the intracellular fluid. D. its volume is slightly less than the plasma compartment. E. its volume decreases when a hypertonic sodium chloride solution is infused intravenously. 5. A patient has 14 L of extracellular fluid (ECF), about 28L of intracellular fluid (ICF) and a plasma osmolarity of 270 mos/l. If 100 ml of a 3000m M/L urea solution were infused intravenously, which of the following is likely to occur (assume no loss through kidneys)? A. about 600 ml of water will move from the ICF to the ECF. B. the new steady-state plasma osmolarity will be 320 mos/l. C. the new steady-state ICF volume will be about 28L. D. the plasma sodium concentration would decrease to 134 meq/l. E. the plasma sodium concentration would increase to 146 meq/l. 6. Six ml of a solution containing 20 mg% Evans Blue were injected into a 120 kg man. Assuming he is in normal fluid balance, his steady-state plasma concentration of Evans Blue would be approximately (in mg/ml): A. 2 x 10-2 B. 2 x 10-3 C. 2 x 10-4 D. 5 x 10-5 E. 5 x Following an intravenous injection of a known amount of an isotope of Ca 2+, the calculated volume of distribution based on the steady-state plasma concentration of the isotope (assuming no loss of the isotope from the body) would be A. equal to the total body water space. B. equal to the ICF volume. C. equal to the ECF volume. D. equal to the volume of the sarcoplasmic reticulum. E. relatively large but have no physiological meaning in terms of a volume measurement.

2 8. A 100 kg subject was injected with 2 ml of a solution containing 30 mg/ml of an inert substance. After equilibration, the plasma concentration of the substance was mg/ml. In the second part of this study the subject was given 100 ml of a solution containing 100 milliosmols of the substance. Which of the following statements would apply: A. In the second part of the study there would be a net water movement from ICF to the ECF. B. The volume of distribution of the substance is the ECF. C. No net water shifts would have occurred between the ICF and the ECF after injection of the 100 m0smoles. D. The agent would be a good plasma expander. E. The osmolarity of the ICF would have increased more than the osmolarity of the ECF in the second part of the study. 9. The following data were obtained in a 100 kg. patient. Amount of X injected = 100 microg Plasma concentration of steady state = 2 microg% Therefore X could have been: A. Na 24 B. Inulin C. Evans Blue D. Urea E. Mannitol 10. In a 70 kg person, the amount of Na in the extracellular fluid is about: A microeq. B microeq. C m Eq. D m Eq. E Eq. 11. The osmolarity of a solution: A. depends on the type of particles in solution. B. depends on the square of the charge on the particles. C. depends on the size of particles in solution. D. is equivalent to its tonicity. E. can be measured in terms of the freezing point depression. 12. An isotonic solution (with respect to red blood cells) A. must contain some protein. B. must contain 150 mm NaC1. C. can be assessed in terms of freezing point depression. D. elicits no net water flow from the cells. E. cannot contain urea. 13. Red blood cells are placed in a solution containing 300 mm urea. Within a few seconds the initially cloudy solution becomes clear. The most likely explanation of this observation is: A. The urea solution is hypertonic and the cells shrink to a very small volume allowing light to pass. B. The urea solution is isotonic but urea dissociates integral membrane proteins. C. The solution is hypotonic due to the high permeability of urea which results in hemolysis of the red blood cell. D. Urea penetrates the cell membrane and dissociates hemoglobin resulting in a transparent cell. E. Red blood cells rapidly come out of suspension due to the effect of urea on surface tension. 14. Which one of the following solutions of identical osmolarity is isotonic with respect to the red blood cell A. 150mM sucrose + 75mM NaC1 B. 150mM urea + 75 mm NaC1 C. 150mM NH 4 C1 D. 300mM urea E. 150mM urea + 75mM NH 4 C1 15. A hypertonic solution A. has less solute particles than are contained in a red blood cell. B. will hemolyze a red blood cell. C. contains urea. D. has a greater effective osmotic pressure than a solution isotonic with a red blood cell. E. none of the above.

3 16. To a suspension of red blood cells in M NaC1, urea is added to bring the urea concentration to 0.3 M. After one minute of stirring the red blood cells would be: A. shrunken to 1/2 the original volume. B. swollen to twice the original volume. C. hemolyzed. D. unchanged. E. shrunken to the same extent as in a 0.3 M NaC1 solution. 17. The transport of glucose into red blood cells occurs by facilitated diffusion. Such a mechanism is characterized by: A. glucose uptake rates greater than that of urea. B. a dependence on ATP. C. a linear dependence on the glucose concentration gradient. D. saturation of the uptake rate at large glucose concentration gradients. E. rates of uptake of d glucose and l glucose being similar. Directions: For each of the questions or incomplete statements below ONE or MORE of the answers or completions given are correct. On the answer sheet, fill in the circle containing A if only 1,2 and 3 are correct B if only 1 and 3 are correct C if only 2 and 4 are correct D if only 4 is corr ect E if ALL are correct 18. Which of the following solutions is/are isotonic with respect to red blood cells? mM sucrose mM NaC mM NaC mM sucrose mm urea mM urea. 19. Osmotic pressure in any system 1. depends on the total number of solute particles. 2. depends on the degree of dissociation of each ionizable solute species. 3. depends on temperature. 4. is inversely related to the concentration of water. 20. Which of the following are isotonic to red blood cells? mM Urea 2. 75mM NaC mM Urea mm NaC mM NaC mM sucrose. 21. The tonicity of a solution 1. is related to the number of impermeant particles of solute. 2. could be predicted from the van't Hoff equation ( osmotic pressure = CRT). 3. is related to the permeability properties of the membrane system to which it is referred. 4. is related to the atmospheric pressure. 22. Which of the following statement(s) regarding osmotic pressure is (are) true? 1. You can calculate the effective osmotic pressure from the total osmolar concentration of blood. 2. The plasma colloid osmotic pressure is likely to be lower than normal in a person with cirrhotic liver. 3. In a steady state, the concentration of solute, expressed either as equivalents or osmoles, is greater inside than outside cells. 4. Within a few minutes following a rapid loss of blood amount to 20% of the total blood volume, you would expect to find a decrease in an individual's plasma colloid osmotic pressure. 23. The following solutions at equilibrium are isotonic with respect to red blood cells mm urea mm urea mm Na Cl mm urea mm urea mm NaCl Answer Key Part 1 1 B 2. A 3. E 4. B 5. C 6. C 7. E

4 8. C 9. C 10. D 11. E 12. D 13. C 14. A 15. D 16. D 17. D 18. A 19. E 20. D 21. B 22. C 23. C Cellular Physiology Part 2 Electrical Events Dr. Judith Heiny Department of Molecular and Cellular Physiology 1. The speed of propagation of an action potential in a nerve fiber is A. independent of membrane permeability B. dependent on the length of the axon. C. dependent on the diameter of the axon. D. independent of the myelination of the axon. 2. If the concentration of K + inside a nerve or skeletal muscle is increased, A. the Na+ gates will open. B. the membrane becomes hyperpolarized. C. the membrane becomes depolarized. D. there will be no effect on Cl movement across the membrane. E. some of the negatively charged proteins leave the axon. 3. During the propagation of the action potential in an unmyelinated neuron, A. electrotonic spread of current causes regions adjacent to the active site to become depolarized. B. all of the Na gates throughout the axon open simultaneously. C. the concentration of the Na inside a cell increases about 25%. D. Cl concentration on the outside of the cell decreases. E. the wave of depolarization jumps from one region of membrane to another. 4. The resting membrane potential A. is significantly affected by the Cl concentration on the outside under steady state conditions. B. can be approximately calculated if one knows the K + concentration inside and outside the cell. C. is totally dependent on the resting Na + permeability. D. can be abolished if the K + concentration inside the cell is increased. 5. When a membrane potential reaches threshold A. an action potential will be created because of Na + inactivation. B. an action potential is produced because the membrane becomes permeable to K +. C. the membrane depolarizes until the Na equilibrium potential is reached. D. the membrane depolarizes then begins to repolarize before the Na+ equilibrium potential is reached. E. more Na + is exchanged for each K + by the Na K pump. 6. At the peak of an action potential: A. The membrane potential is equal to the sodium equilibrium potential. B. The membrane potential does not reach the sodium equilibrium potential because potassium conductance has already started to increase. C. The membrane potential does not reach the sodium equilibrium potential because the sodium channel moves back to the closed state during the rising phase of the action potential. D. Sodium concentration inside and outside the membrane is equal.

5 7. In myocardial cells, [K] i is 160 mm and [K] o is 4 mm. Therefore, the K + equilibrium potential (E K ) would be closest to which value (at 37 o C): Use the following approximate A. -60 mv log table: B. +60 mv N log N C. -80 mv D. -98 mv E mv deteted 9 deleted 10. Membrane ionic permeability A. refers to the lipid portion of the membrane. B. increases because the average pore diameter of a given population of ion channels increases. C. refers to the ease with which ions pass through a membrane. D. decreases when the number of open ion channels per unit area of membrane increases. E. refers to the electrical resistance of the axoplasm. 11. The refractory phase of an action potential A. is due to an increase in permeability to Cl. B. is due to Na inactivation. C. is due to a decrease in permeability to K. D. is not found in peripheral axons. 12. The total electrochemical driving force for net Na + influx into a nerve fiber at the start of an action potential is closest to which value: A. 0 mv B mv C mv D mv E mv 13. The resting membrane potential of nerve fibers is closest to the equilibrium potential for which ion: A. K + B. Na + C. Ca ++ D. H + E. PO deleted 15. Assuming Cl ion to be passively distributed in mammalian skeletal muscle fibers, if [Cl] o is 120 mm and [Cl] i is 6 mm in fibers at rest, the resting potential of this cell would be closest to which value (at 37 o C): Use the following approximate A. +50 mv log table: B. -70 mv N log N C. -80 mv D. -90 mv E mv

6 16. The rising (depolarizing) phase of the nerve action potential is due to which one of the following: A. increase in K + permeability. B. decrease in K + permeability. C. decrease in Ca ++ permeability. D. increase in Cl - permeability. E. increase in Na + permeability. 17. To produce the all or none action potential in neurons, there is a positive feedback relationship between the membrane potential and: A. Cl permeability. B. K + permeability. C. Na + permeability. D. Ca ++ permeability. E. intracellular Na+ concentration ([Na] i ). 18. Which of the following variables are in balance at the equilibrium potential for an ion? A. the intracellular and extracellular concentrations of the ion. B. the diffusional gradient and the electric field. C. the sodium concentration inside the cell and the potassium concentration outside the cell. D. the positive charges on each side of the membrane capacitance. E. the potassium concentration inside the cell equals the chloride concentration outside the cell. 19. If the extracellular potassium concentration increases to 16 mm, and the intracellular potassium concentration remains constant at 160 mm, what will be the new resting membrane potential (in mv)? A. +61 log10 (0.1) = -1 B. -61 log10 (1) = 0 C log10 (10) = 1 D log10 (62) = 1.8 E log10 (100) = During the fast rising phase of the skeletal muscle action potential, sodium ions move into the cell through sodium channel proteins. As the cell membrane depolarizes from a resting potential of about -100 mv to near the sodium equilibrium potential of +70 mv, approximately how manysodium ions per square centimeter of membrane enter the cell? A. 10 millimoles/cm 2 (10 x 10-3 Moles/cm 2 ) B. 1.7 millimoles/cm 2 (1.7 x 10-3 Moles/cm 2 ) C. 1.7 micromoles/cm 2 (1.7 x 10-6 Moles/cm 2 ) D. 1.7 picomoles/cm 2 (1.7 x Moles/cm 2 ) E. 1.0 femtomoles/cm 2 (1.0 x Moles/cm 2 ) 21. The resting membrane potential of skeletal muscle fibers is near the potassium equilibrium potential because: A. the sodium potassium ATPase maintains the intracellular potassium concentration greater than the extracellular sodium concentration. B. the resting membrane is permeable primarily to potassium ions and the K+ concentrations are not equal inside and outside the cell. C. sodium channels are inactivated. D. the potassium equilibrium potential is more negative than the sodium equilibrium potential. E. there is a small excess of positive charges on the inside of the membrane. 22. The resting potential of cells arises because: A. The sodium potassium ATPase concentrates K + ions inside the cell and K + cannot leak back out; this results in an ICF electrically negative with respect to the ECF. B. The diffusional gradient acting on a K + ion and tending to move it into the cell is exactly balanced by an electrical potential differenceacting to attract the K + ion back out of the cell. C. The diffusional gradient acting on a K + ion and tending to move it out of the cell is exactly balanced by an electrical potential differenceacting to attract the K + ion back into the cell. D. The sodium potassium ATPase transports 2 K + ions into the cell for every 3 Na + ions it transports out during each pump cycle. Consequently, the ICF becomes deficient in positive charged ions, and is electrically negative with respect to the ECF. E. The diffusional gradient acting on a Na + ion and tending to move it into the cell is exactly balanced by an electrical potential differenceacting to attract the Na + ion back out of the cell.

7 23. A drug opens sodium channels so that instead of being mostly closed at rest, they open and make the total resting sodium permeability equal to the total resting potassium permeability of the cell. In the presence of this drug, the resting membrane potential would (compared to control): A. stay the same B. depolarize to a value close to E Na. C. hyperpolarize to a value half way between E K and E Na. D. depolarize to a value half way between E K and E Na. E. reach a value close to E K. 24. The drug digatalis blocks the activity of the sodium potassium ATPase pump. Consequently, when it is given to a patient, the K+ concentration of the ICF decreases slightly while the K + concentration of the ECF increases. Assuming no other changes, if the concentrations of K + in the ECF increased from 4 to 8 mm, and that of the ICF decreased from 140 to 135 mm, the resting membrane potential would: A. hyperpolarize to -96 mv. B. depolarize to - 75 mv. C. hyperpolarize to -180 mv. D. depolarize to +75 mv. E. hyperpolarize to -93 mv. 25. Which of the following statements regarding the resting membrane potential is true: A. There is a small excess of unpaired K + ions near the outer membrane surface and the same number of unpaired anions near the inner membrane surface. B. There is a small excess of unpaired anions near the outer membrane surface and an equal number of unpaired K+ + ions near the inner membrane surface. C. There is a small excess of free unpaired K + ions distributed throughout the external solution (ECF), and an equal number of unpaired anions distributed throughout the internal solution (ICF). D. Bulk electroneutrality of both the ECF and ICF is not maintained. E. There is a small excess of free unpaired K + ions distributed throughout the internal solution (ICF), and an equal number of unpairedanions distributed throughout the external solution (ECF). Directions: For each of the questions or incomplete statements below ONE or MORE of the answers or completions given are correct. On the answer sheet, fill in the circle containing A if only 1,2 and 3 are correct B if only 1 and 3 are correct C if only 2 and 4 are correct D if only 4 is correct E if ALL are correct 26. deleted 27. An action potential in the nerve axon 1. can be produced if the membrane is rapidly depolarized above -60 mv. 2. is produced when there is a sudden increase in the permeability of the membrane to Na + ions. 3. is an all or none response that propagates without degradation. 4. is blocked as soon as the activity of the Na pump is blocked. 28. During the production of an action potential 1. the permeability of the membrane to Na + increases transiently and then returns to near baseline. 2. the polarity of the membrane potential reverses. 3. the Na + inactivation process prevents the overshoot of the action potential from reaching the Na + equilibrium potential. 4. the K + permeability increases followed by an increase in permeability to Na If the Na inactivation process is inhibited and the neuron is then stimulated above threshold 1. excitation will not occur. 2. the permeability to K + will decrease. 3. the peak of the action potential will be less than one. 4. the membrane remains depolarized following the rising phase of the action potential.

8 30. The charges separated across the cell membrane 1. represent a very small proportion of the cellular ionic content. 2. can be calculated from the membrane capacitance and voltage. 3. produce an electrical potential difference across the membrane. 4. cause the intracellular and extracellular fluids to deviate from bulk electroneutrality. 31. An intravenous injection of KCl given to an experimental animal elevated the plasma K + concentration to 15 mm. Which of the following would result: 1. partial depolarization of nerve and muscle cells. 2. decreased maximal rate of rise of the action potentials (V max ). 3. slowed conduction velocity and blockage of transmission in nerve and muscle cells. 4. hyperpolarization of all nerve and muscle cells. 32 The falling (repolarizing) phase of the skeletal muscle action potential is due to which of the following: 1. increase in K + conductance. 2. decrease in Na + conductance. 3. Cl influx. 4. increase in Ca ++ conductance. 33. At the peak of the skeletal muscle action potential, the membrane potential becomes positive because: 1. the sodium concentration inside the cell exceeds the potassium concentration inside the cell. 2. the Na + influx through Na + channels produces a slight excess of positive charges on the inside of the membrane. 3. the sodium potassium ATPase is temporarily turned off. 4. the membrane potential approaches the Na + equilibrium potential. 34. During the falling phase of the skeletal muscle action potential, which of the following events return the membrane potential to the resting value? 1. sodium channels spontaneously inactivate after opening. 2. voltage-dependent delayed potassium channels open. 3. the membrane potential approaches the potassium equilibrium potential. 4. calcium channels open. 35. During the falling phase of the nerve and skeletal muscle action potential, which of the following phenomena contribute to the repolarization of the membrane? 1. sodium channels are inactivating. 2. chloride channels are closing. 3. delayed potassium channels are opening. 4. resting potassium channels are closing. 36. During the rising phase of the cardiac action potential, the membrane depolarizes because: 1. Resting K + channels close and the K+ ions can no longer influence the membrane potential. 2. Sodium channels open and a very small number of Na + ions enters the cell. These ions change the charge balance on the membrane surface, such that the inner surface now has a slight excess of Na + ions, while the outer surface is left with a slight excess of unpaired anions. 3. Sodium channels open. At this point, the membrane potential is far away from E Na and there is a driving force for Na + ions to enter thecell. Consequently, Na + current flows until Em approaches E Na. 4. The sodium potassium ATPase rapidly shuts down. This causes the K + concentration of the ECF to rise and brings E m to a new, depolarized value. 37. In a patient who has to rely on a functioning artificial pacemaker to maintain his heart rate at 70 beats per minute, the excitability of his heart muscle is of importance. An increase in which of the following would interfere with the proper function of the artificial pacemaker? A. extracellular Cl concentration. B. intracellular Ca ++ /Na + ratio. C. extracellular Ca ++ concentration. D. intracellular K + concentration. E. extracellular K + concentration. Answer Key Part2 1. C 2. B 3. A 4. B 5. D 6. B 7. D 8. deleted 9. deleted 10. C 11. B 12. D 13. A 14. deleted 15. C 16. E 17. C 18. B 19. B 20. D 21. B 22. C 23. D 24. B 25. A 26. deleted 27. A 28. A 29. D 30. A 31. A 32. A 33. C 34. A 35. B 36. A 37. E

9 MEDICAL PHYSIOLOGY: SECTION II (PHYSIOLOGY OF MUSCLE) Dr. Richard Paul Department of Molecular and Cellular Physiology 1. One of the following state,emts is not consistent with the relation between the force and shortening velocity in muscle. A. With an afterload of 1/2 the maximum isometric force, the speed is considerably less than 1/2 maximum. B. At 1/2 the maximum speed of shortening, the force the muscle can generate is considerably greater than 1/2 the isometric force. C. Muscles contract only at very slow speeds when exerting near maximal loads. D. The number of cycling cross bridges may increase with load. E. The relation between shortening speed and load is hyperbolic. 2. A skeletal muscle treated with a drug that specifically inhibits oxidative metabolism would, in an acute experiment A. not be able to contract. B. support short bursts of activity. C. be very resistant to fatigue. D. have an abnormal force length relation. E. not propagate action potentials. 3. Which of the following statements contrasting skeletal and smooth muscle is false: A. Smooth muscle cells are considerably smaller than skeletal muscle cells. B. The filaments in smooth muscle are less ordered than the sarcomere repeating unit of skeletal muscle. C. Activation of smooth muscle contraction does not depend on intracellular Ca + +. D. The rate of ATP hydrolysis required for contraction in smooth muscle is much less than in skeletal muscle. E. Smooth muscle has no T tubule system and the sarcoplasmic reticulum is much less extensive. 4. The decrease in active isometric force found to occur at long muscle (sarcomere) lengths can be best attributed to: A. failure of Ca ++ to remove the troponin tropomyosin inhibition of actin myosin interaction. B. realignment of myofibrils. C. reduction in the number of available actin-myosin interaction sites. D. failure of action potentials to propagate. E. disruption of T tubule system. 5. Which of the following statements about smooth muscle is true? A. contractions are not dependent on calcium. B. readily fatigues. C. cells are generally larger than skeletal muscle cells. D. contraction is regulated by proteins contained on the thick filament. E. is smooth because of a lack of thick and thin filaments. 6. The plateau region found in the active isometric force vs. length relation in skeletal muscle can be best attributed to: A. An increase in excitation contraction coupling offsetting the inherent loss of isometric force with length. B. The increase in passive force with length. C. The constant number of crossbridges available for interaction due to the structure of the thick filament. D. The fact that muscle metabolism is relatively independent of muscle length. E. The fact that a muscle is generally composed of mixed fiber types. 7. Which of the following statements concerning the crossbridge cycle is true? A. relative filament motion is generated by shortening of actin subunits. B. one ATP molecule is hydrolyzed. C. one lactate molecule is produced. D. troponin is regenerated from tropomyosin. E. actin and myosin do not come into contact. 8. A brief exposure to a hypotonic solution can selectively destroy the t tubule system in skeletal muscle. Assuming that only the t tubule system is destroyed, such a muscle would: A. not be able to generate action potentials. B. be characterized by low phosphocreatine levels. C. be unable to develop a normal contractile response to electrical stimulation. D. be unable to relax following stimulation. E. have a greatly enhanced velocity of shortening. 9. The relation between velocity of shortening and load in muscle A. is a consequence of A band shortening. B. indicates that contraction speed increases rapidly with increases in load. C. suggests that less crossbridges are able to interact per unit of time as contraction speed increases.

10 D. is a consequence of the geometry of the longitudinal and transverse tubule system. E. is linear. 10. A decline in the capacity of muscle to generate active isometric force at sarcomere lengths longer than 2.5 microns can be primarily attributed to the A. reduction in overlap between thick and thin filaments. B. lengthening of the thick filament. C. enhancement of Ca ++ uptake by the sarcoplasmic reticulum. D. inhibition of ATP synthesis. E. disruption of the t tubule system. 11. Barbiturates are known to lower the rate of uptake of Ca ++ by the sarcoplasmic reticulum. The most likely effect of barbiturates on skeletal muscle would be to A. block the propagation of action potentials. B. slow down the rate of relaxation. C. alter the active force length relation. D. inhibit glycolysis. E. disrupt thick filament organization. 12. The molecular mechanism by which Ca ++ activates mammalian skeletal muscle involves the A. binding of Ca ++ to the thick filament. B. binding of Ca ++ to troponin. C. binding of Ca ++ to tropomyosin. D. direct activation of C protein. E. enhancement of Cl permeability of the sarcoplasmic reticulum. 13. At very long muscle lengths (relative to body length), the total force a muscle can exert increases steeply with further increases in length. This reflects A. loss of function of the sarcoplasmic reticulum at long lengths. B. an increase in the number of actin myosin sites. C. a release of myosin light chain kinase from the thin filament. D. the force length characteristics primarily of passive structures in muscle. E. enhancement of excitation contraction coupling. 14. Smooth muscle in general is characterized by slower contraction speeds and a higher efficiency of force maintenance (i.e., lower rate of ATP utilization per unit force) than skeletal muscle. This is related to: A. a lower cross bridge cycling rate as indicated by a lower actomyosin ATPase activity in smooth muscle. B. the lack of a t tubule system in smooth muscle. C. differences in the force length relation. D. the smaller creatine phosphate concentration characteristic of smooth muscle. E. a contractile mechanism in smooth muscle based on folding of contractile filaments. 15. Your patient can sustain low levels of muscular activity but complains of pain and weakness when attempting moderately high levels of muscular activity. A possible diagnosis would be: A. absence of acetylcholinesterase. B. mitochondrial defect. C. high levels of phosphocreatine. D. Troponin subunit irregularities. E. defect in glycolytic metabolism. 16. Muscular contraction requires energy in the form of ATP. The process responsible for the major utilization of ATP during contraction is: A. restoration of A band to original length B. maintenance of Na + and K + gradients C. maintenance of a depolarized state D. crossbridge cycling E. thin filament folding 17. Ca ++ is required for activation of striated muscle. The mechanism involves: A. reorientation of the Z band. B. fusion of the t tubule and sarcoplasmic reticulum at the triad junctions. C. movement of the myosin heads away from the thick filament axis. D. removal of the inhibition of the tropomyosin troponin complex on actin myosin interaction. E. all of the above.

11 18. The total isometric force vs. length relation differs between striated muscles primarily because: A. The passive force length characteristics differ. B. Sarcomere length varies greatly. C. Muscle activation is quite variable. D. The relative contribution of glycolytic to oxidative metabolism varies. E. The extent of the sarcoplasmic reticulum is variable. 19. Relaxation in skeletal muscle occurs when: A. The t tubule system becomes refractory. B. Intracellular Ca ++ is reduced below 10 8 M by uptake into the sarcoplasmic reticulum. C. Tropomyosin dissociates into subunits. D. The supply of cellular ATP is exhausted. E. The action potential duration shortens. 20. On the molecular level, the role of Ca ++ in regulation of muscle contraction can be best ascribed to: A. The effect of Ca ++ on the assembly of myosin molecules into thick filaments. B. The shortening of the thin filament in the presence of Ca ++. C. The effect of Ca ++ on propagation of action potentials. D. The effect of Ca ++ on metabolism. E. The b inding of Ca ++ to troponin and subsequent removal of the inhibition of tropomyosin on actomyosin interaction. 21. A genetic defect in muscle resulting in severe inhibition of glycolytic metabolism would be expected to cause: A. An altered filament structure. B. An insensitivity to normal Ca ++ levels. C. An inability to acute perform strenuous exercise with no apparent effects on light muscular activity. D. An impairment of prolonged low level muscular activity with no apparent effect on strenuous exercise. E. An inhibition of contraction in B fibers. 22. The relation between force and velocity in muscle: A. Is linear. B. Is a consequence of the dependence of the A band length on sarcomere length. C. Suggests that more crossbridges interact at high contraction velocities. D. Indicates that velocity is relatively independent of load. E. Indicates that speed of contraction decreases rapidly with load. 23. During a single crossbridge cycle: A. one ATP molecule is hydrolyzed. B. relative filament motion is generated when a myosin molecule binds to a thick filament. C. actin and myosin do not come into contact. D. thin filaments shorten and force is generated. E. myosin is cleaved from a tropomyosin precursor. 24. The relation between force and velocity in muscle: A. is dependent on fibre type. B. is linear. C. indicates that the load bearing capacity decreases rapidly with speed of contraction. D. is related to t tubule distribution. E. is a consequence of the dependence of A band length on sarcomere length. 25. Certain muscular dystrophies are characterized by a moderate loss of actin and myosin in the muscle. One would anticipate these muscle cells would A. show a loss of excitability. B. have a prolonged twitch duration. C. be impossible to tetanize. D. lose calcium sensitivity. E. generate less force than normal cells. 26. Certain drugs can selectively inhibit glycolytic metabolism in muscle. Such drugs would have a strong effect on A. ability of myosin molecules to assemble into filaments B. ability to maintain posture. C. a single isometric twitch. D. resistance to fatigue of white muscle (A fibers, FG). E. ability to generate an action potential in a muscle cell.

12 27. Barbiturates are known to lower the rate of uptake of Ca ++ by the sarcoplasmic reticulum. The most likely effect of barbiturates on skeletal muscle would be: A. to prevent propagation of an action potential. B. disrupt conduction in the transverse tubule system. C. prolong the duration of an isometric twitch. D. increase the tetanic isometric force. E. inhibit glycolysis. 28. Treatment of a muscle with hypertonic solutions can selectively destroy the t tubule system. The effect of destruction of the t tubule system on skeletal muscle would be to: A. cause an irreversible contraction. B. block muscle contraction when stimulated in spite of measured membrane action potentials. C. stimulate oxidative metabolism. D. alter the passive force length relation. E. prolong twitch duration and potentiate the force measured in an isometric twitch. 29. During a single cross bridge cycle A. several ATP molecules are hydrolyzed. B. relative filament motion is generated when a myosin molecule bound to actin changes its conformation to that found in rigor. C. actin and myosin do not come in contact. D. thick filaments shorten and force is generated. E. tropomyosin is cleaved from a troponin molecule. 30. T tubules are characteristic of skeletal muscle but absent in mammalian smooth muscle; this is best related to A. lack of striations in smooth muscle. B. a somewhat larger thick filament in smooth muscle than skeletal muscle. C. approximately 10 fold greater diameter of skeletal muscle compared to smooth. D. smooth muscle can maintain more isometric force per myosin than skeletal muscle. E. Ca ++ is required to activate both types of muscle. 31. Phosphorylation of certain proteins in the sarcoplasmic reticulum can enhance its rate of Ca ++ uptake. The most likely effect of substances which promote this effect (ex. beta adrenergic agonists) would be to: A. increase the velocity of the spread of the action potential. B. inhibit lactate production but not oxygen consumption. C. shorten the duration of a single isometric twitch. D. slow the rate of aggregation of thin filaments. E. decrease the rate of A band shortening. 32. Feeding rats on a diet which includes beta guanidino proprionic acid will eliminate nearly all phosphocreatine. Assuming that no other metabolic dysfunction occurs, skeletal muscle from these animals might be expected to show: A. a hypersensitivity to Ca ++ at long muscle lengths relative to the in vivo length. B. an inability to relax. C. low levels of muscle activity would appear normal, but intensive muscle activity would be impaired. D. spontaneous contractions. E. a loss of striations. Directions: For each of the questions or incomplete statements below ONE or MORE of the answers or completions given are correct. On the answer sheet, fill in the circle containing A if only 1, 2 and 3 are correct B if only 1 and 3 are correct C if only 2 and 4 are correct D if only 4 is correct E if ALL are correct 33. During a single crossbridge cycle: 1. An ATP molecule binds to a complex consisting of an actin molecule and a myosin head. 2. The actin myosin complex is dissociated. 3. The ATP molecule is hydrolyzed on the myosin head. 4. A relative sliding of about 1 micrometer between thick and thin filaments occurs. 34. A certain class of drugs is descriptively known as "Ca ++ entry blockers". Assuming that their primary effects is to inhibit transmembrane Ca ++ flux, one would expect: 1. Relatively little effect on skeletal muscle. 2. Major effects on skeletal muscle. 3. Major effects on smooth muscle. 4. Little effect on smooth muscle. 35. Smooth muscle: 1. Does not contain a t tubule system.

13 2. Does not contain thick filaments. 3. Does not readily fatigue. 4. Contractions are independent of Ca Factors that can influence force in smooth muscle include: 1. intracellular Ca ++ concentration. 2. the phosphorylation state of myosin. 3. the phosphorylation state of myosin light chain kinase. 4. contraction velocity. 37. The generation of a contractile force in a whole muscle in the intact organism may depend on: 1. the number and location of motor units stimulated. 2. the stimulation frequency to an individual motor unit. 3. the isometric twitch time. 4. the length of the muscle 38. Relaxation of skeletal muscle is associated with 1. a refractory state of the t tubule system 2. intracellular Ca ++ reduction below 10 8M 3. an exhaustion of cellular ATP stores 4. dissociation of Ca ++ from troponin 39. The force a skeletal muscle is able to generate is related to the: 1. number of activated cross bridges. 2. sarcomere length 3. shortening velocity 4. stimulation frequency 40. Ca ++ plays a central role in skeletal muscle contraction as it: 1. underlies the mechanisms coupling electrical depolarization of the sarcolemma with contraction. 2. is the major current carrying ion during the rapid depolarization phase of the action potential. 3. binds to troponin effecting the release of tropomyosin inhibition of actomyosin interaction. 4. binds to tropomyosin so that the actomyosin interaction is inhibited and relaxation occurs. 41. Isometric force in a whole muscle would depend on: 1. number of fibers recruited. 2. length of the muscle. 3. stimulation frequency. 4. twitch duration of fibers. 42. "A" (FG) type muscle fibers have the following characteristics: 1. are large compared to other fiber types. 2. depend primarily on glycolytic metabolism. 3. are fast compared to other fiber types. 4. are highly resistant to fatigue. 43. Purified actin and myosin when mixed together: 1. will not act as an ATPase unless Ca ++ is present at (10 6 M). 2. spontaneously bind to form a highly bound complex. 3. are dissociated by Ca precipitate out of solution when ATP is added. 44. The following observations are crucial to the development of the sliding filament mechanism proposed for muscle contraction: 1. relation between active isometric force and muscle length. 2. change in the banding pattern seen with optical microscopy during contraction. 3. constant length of thick and thin filaments observed by electron microscopy at various sarcomere lengths. 4. hyperbolic relation between velocity and tension. 45. A hypothetical muscle disorder involves the reduction in the capacity for oxidative phosphorylation. Which symptom(s) would likely characterize this condition? 1. loss of fatigue resistance of red muscle (predominantly B fibers). 2. inability to perform even short durations of maximal muscle activity. 3. poor performance in marathon races. 4. coordination of muscular activity would be difficult.

14 46. The generation of maximal force in the biceps would involve 1. an increase in the frequency of firing of individual motor units. 2. inhibition of small motor units. 3. activation of large motor units. 4. total synchronization of individual cross bridge movements. 47. Smooth muscle contraction velocity is substantially slower than skeletal muscle. This is likely to be due to 1. lack of a t tubule system in smooth muscle. 2. fundamental differences in the active force length relations of the two muscle types. 3. lack of striations in smooth muscle. 4. low actomyosin ATPase and the related increase in cross bridge cycle duration in smooth muscle. 48. Myotonia congenita is a rare hereditary disease in which the resting Cl conductance (g Cl ) of skeletal muscle is abnormally low. This condition leads to repetitive firing of muscle action potentials because 1. the high g Cl of normal muscle tends to clamp V m near 90 mv and prevent refiring. 2. the low g Cl of myotonic fibers induces hyperpolarization and tetanus. 3. in the absence of high g Cl, extracellular K + accumulation in T tubules during action potentials can cause depolarization and refiring. 4. the high g Cl of normal muscle is necessary to prevent a large electrogenic pump potential. 49. The addition of ATP to a solution of purified skeletal muscle myosin, actin, and troponin results in: 1. an initial rapid clearing followed by "superprecipitation". 2. a dissociation of troponin from myosin. 3. an increase in the ATPase. 4. formation of a "rigor complex" between actin and myosin. Answer Key Muscle 1. B 2. B 3. C 4. C 5. D 6. C 7. B 8. C 9. C 10. A 11. B 12. B 13. D 14. A 15. E 16. D 17. D 18. A 19. B 20. E 21. C 22. E 23. A 24. C 25. E 26. D 27. C 28. B 29. B 30. C 31. C 32. C 33. A 34. B 35. B 36. E 37. E 38. C 39. E 40. B 41. E 42. A 43. C 44. A 45. B 46. B 47. D 48. B 49. B