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Passage 1

Blood flow to the brain is regulated by changes in arterial vessel diameter in response to intravascular pressure, a process called the myogenic response (MR). The MR allows cerebral resistance vessels to achieve a state of partial constriction, from which they can dilate or further constrict to alter blood flow.

Vascular smooth muscle (VSM) contraction is initiated by cell membrane depolarization, which opens voltage-gated calcium channels. Calcium ions bind the cytosolic protein calmodulin, which activates an enzyme that phosphorylates amino acid residue 19 of the myosin light chain (LC20). Phosphorylation of LC20 is required to activate the myosin head, which binds to actin. This myosin–actin interaction forms the basis of the cross-bridge cycle (CBC), which causes muscle contraction, as in skeletal muscle.

Dynamic reorganization of the actin cytoskeleton occurs during VSM contraction and relaxation. During actin polymerization, monomers of globular actin (G-actin) polymerize into filamentous actin (F-actin). Actin depolymerization can be induced by the drug latrunculin B.

To examine changes that occur in VSM during the MR, researchers exposed isolated rat middle cerebral arteries (RMCA) to increasing internal pressure to mimic intravascular changes that would occur in vivo. Arterial diameter, and the amounts of phosphorylated LC20, phosphorylated calponin (phosphorylation of calponin reduces its inhibition of the actin-activated myosin MgATPase), and G-actin were determined in response to a three-step pressurization from 10 to 80 to 120 mmHg (Table 1).

Table 1 Changes in RMCA Diameter and Protein Levels in Response to Artificially Adjusted Internal Pressure

Variables Internal pressure
10 mmHg 80 mmHg 120 mmHg
Arterial diameter (µm) 225 193 175
Phosphorylated LC20 (%) 21 50 52
Phosphorylated calponin (%) 7 18 18
G-actin (amount) 1 0.3† 0.1†

Note: † indicates data are normalized to 10 mmHg value.

Adapted from I. Kimura, K. Ozawa, D. Inoue, T. Imamura, K. Kimura, et al., Nature Communications ©2013 Nature Publishing Group.

Questions

1. Based on the information in the passage, which type of enzyme is most likely to suppress CBC?

  1. Phosphorylase
  2. Kinase
  3. Phosphatase
  4. Synthase

2. Which statement regarding VSM function and cytoskeletal dynamics is best supported by the data in Table 1?

  1. Vasoconstriction is associated with an increase in the ratio of F-actin to G-actin.
  2. F-actin levels decrease as phosphorylation of LC20 increases.
  3. Vasodilation does not affect phosphorylation levels of calponin.
  4. Arterial diameter reduction is always dependent upon increased calponin phosphorylation.

3. Compared to control RMCA held at an internal pressure of 120 mmHg, application of latrunculin B to RMCA held at 120 mmHg will most likely result in:

  1. increased phosphorylated LC20 levels.
  2. decreased arterial diameter.
  3. decreased F-actin levels.
  4. increased phosphorylated calponin levels.

4. According to the information in the passage, which statement best describes the function of the MR in response to stimulation of the sympathetic nervous system? The MR:

  1. equalizes blood pressure in cerebral resistance arteries and the aorta.
  2. moderates blood flow to the brain under high pressure.
  3. enables cerebral resistance arteries to locally vasodilate.
  4. redirects blood circulating in the brain to organs in the abdominal cavity.

5. The polymerization of which structural component was analyzed in the experiment described in the passage?

  1. Microtubules
  2. Microfilaments
  3. Intermediate filaments
  4. Thick filaments

6. What is the likely structure of the amino acid found at position 19 of LC20?

Answers

Question 1 Solution: The correct answer is C. This is a Biochemistry question that falls under the content category “Structure and function of proteins and their constituent amino acids.” The answer to this question is C because the passage states that cross-bridge cycling (CBC) requires phosphorylation of the myosin light chain (LC20). A phosphatase is an enzyme that removes a phosphate group from its substrate; therefore it is likely to suppress CBC. It is a Knowledge of Scientific Concepts and Principles question because it requires the application of assumed knowledge of enzyme types.
Question 2 Solution: The correct answer is A. This is a Biology question that falls under the content category “Structure and integrative functions of the main organ system.” The answer to this question is A, because in the data from Table 1, vasoconstriction is indicated by a decrease in arterial diameter during the pressurization steps. During these steps, the relative amount of G-actin decreases. As the passage states that monomers of G-actin polymerize into F-actin, this means that the ratio of F-actin to G-actin has increased. B is incorrect because F-actin levels increase with each pressurization step when the phosphorylation levels of LC20 also increase. C is incorrect because vasodilation was not tested in this experiment. At each pressurization step, there was an increase in internal pressure which resulted in vasoconstriction. D is incorrect because phosphorylation of calponin did not change between the pressurization steps at 80 and 120 mmHg when a reduction in arterial diameter occurred. It is a Data-based and Statistical Reasoning question because it requires understanding the data in Table 1.
Question 3 Solution: The correct answer is C. This is a Biology question that falls under the content category “Structure and integrative functions of the main organ system.” The answer to this question is A, because in the data from Table 1, vasoconstriction is indicated by a decrease in arterial diameter during the pressurization steps. During these steps, the relative amount of G-actin decreases. As the passage states that monomers of G-actin polymerize into F-actin, this means that the ratio of F-actin to G-actin has increased. B is incorrect because F-actin levels increase with each pressurization step when the phosphorylation levels of LC20 also increase. C is incorrect because vasodilation was not tested in this experiment. At each pressurization step, there was an increase in internal pressure which resulted in vasoconstriction. D is incorrect because phosphorylation of calponin did not change between the pressurization steps at 80 and 120 mmHg when a reduction in arterial diameter occurred. It is a Data-based and Statistical Reasoning question because it requires understanding the data in Table 1.
Question 4 Solution: The correct answer is B. This is a Biology question that falls under the content category “Structure and functions of the nervous and endocrine systems and ways in which these systems coordinate the organ systems.” The answer to this question is B because the MR is a local response in resistance vessels that would slow blood flow to the brain to reduce the chance of tissue damage from high blood pressure resulting from activation of the sympathetic nervous system. A is incorrect because blood pressure is higher in the aorta than in the rest of the body; therefore, blood pressure in the brain and aorta would not be equalized. C is incorrect because the data in Table 1 indicate that increases in blood pressure result in vasoconstriction, not vasodilation. D is incorrect because during activation of the sympathetic nervous system blood flow is directed towards the brain and skeletal muscles, and not to organs in the abdominal cavity. It is a Scientific Reasoning and Problem Solving question because you are asked to predict how the myogenic response will function in response to sympathetic nervous system activation.
Question 5 Solution: The correct answer is B. This is a Biology question that falls under the content category “Assemblies of molecules, cells, and groups of cells within single cellular and multicellular organisms.” The answer to this question is B because microfilaments are composed of actin. It is a Knowledge of Scientific Concepts and Principles question because it requires assumed knowledge.
Question 6 Solution: The correct answer is D. This is a Biochemistry question that falls under the content category “Structure and function of proteins and their constituent amino acids.” The answer to this question is D because of the residues shown only serine can be phosphorylated. It is a Knowledge of Scientific Concepts and Principles question because it requires assumed knowledge of amino acid structure.