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Chapter 6: Molecular and Cellular Biology of the Heart

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?

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

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

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

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

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

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

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

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

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

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

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

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

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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