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Chapter 6: Molecular and Cellular Biology of the Heart

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A 55-year-old man presents with exertional dyspnea and a 10 lb weight gain. His physical exam is notable for an elevated jugular venous pressure, a soft apical holosystolic murmur, and an S3 gallop. Echocardiography reveals a dilated left ventricle with an ejection fraction of 35%. Which of the following is most likely true regarding β-adrenergic signaling in this patient?

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A. β2-adrenergic receptors (β2-AR) are the dominant type of β-adrenergic receptor in the heart

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B. An increase in GRK2 activity contributes to β-adrenergic receptor desensitization

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C. β1-AR density is increased in this patient’s myocytes

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D. This patient’s heart is more sensitive to β-agonists now than before developing decompensated heart failure

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E. β1-AR signaling is likely to protect against apoptosis in his cardiomyocytes

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The answer is B. (Hurst’s The Heart, 14th Edition, Chap. 6) This patient presents with classic findings of heart failure with reduced ejection fraction. In the normal heart, 60% to 80% of β-adrenergic receptors are of the β1 subtype.1 With heart failure, β1-AR is downregulated, and the β1-AR/β2-AR ratio nearly normalizes (options A and C).2 A molecular hallmark of heart failure is the desensitization of the β-adrenergic signaling axis. A failing heart is less sensitive to exogenous β-AR ligands than is a normal heart (option D). At the molecular level, this occurs by a decreased density of β1-AR in cardiomyocytes and increased levels of GRK2. GRK2 phosphorylates β-ARs and reduces their sensitivity (option B).3 Chronic β-AR signaling through the β1-AR is believed to contribute to cardiomyocyte apoptosis seen in heart failure (option E).3

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Which of the following is incorrect regarding excitation–contraction coupling?

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A. Depolarization of the cardiomyocyte membrane results in the opening of L-type calcium channels

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B. The SERCA ATPase functions to sequester calcium in the sarcoplasmic reticulum during relaxation

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C. In a healthy heart, tachycardia results in decreased calcium in the cytoplasm of the cardiomyocyte and increased contractile force

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D. PKA and CaMKII maintain SERCA activity by phosphorylating and inactivating phospholamban

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E. The efficiency of the ryanodine receptor response to cytoplasmic calcium is dependent on the ryanodine receptor’s proximity to the L-type calcium channel

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The answer is C. (Hurst’s The Heart, 14th Edition, Chap. 6) Following depolarization of the cardiomyocyte membrane, L-type calcium channels open, and calcium influxes into the cardiomyocyte (option A).4 In response, ryanodine receptors release calcium from the sarcoplasmic reticulum. The net result ...

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