A 44-year-old man with progressive dyspnea is diagnosed with dilated cardiomyopathy. Despite optimal medical therapy, he continues to have symptoms and disease progression is noted. He undergoes cardiac transplantation after a suitable donor becomes available. Permission is obtained from the patient to study his diseased heart for intracellular calcium regulation. Microelectrodes placed into cardiac muscle cells detect a rapid decrease in cytoplasmic calcium level immediately preceding relaxation. Which of the following proteins is most likely responsible for the observed change in electrolyte levels?

Question

A 44-year-old man with progressive dyspnea is diagnosed with dilated cardiomyopathy.  Despite optimal medical therapy, he continues to have symptoms and disease progression is noted.  He undergoes cardiac transplantation after a suitable donor becomes available.  Permission is obtained from the patient to study his diseased heart for intracellular calcium regulation.  Microelectrodes placed into cardiac muscle cells detect a rapid decrease in cytoplasmic calcium level immediately preceding relaxation.  Which of the following proteins is most likely responsible for the observed change in electrolyte levels?

Quizplus · Accepted Answer

11ec160b_3c9c_4c0c_9249_433f0ece0e10_MD0001_00 Intracellular calcium regulation plays an important role in excitation-contraction coupling. Voltage-dependent calcium channels (L-type) are activated during phase 2 of cardiac action potential (depolarization) and permit influx of calcium into the cardiac myocytes (Choice E). This initial calcium influx is sensed by the ryanodine receptors in the sarcoplasmic reticulum, which triggers further release of Ca²⁺ (calcium-induced calcium release) into the cytoplasm, thereby increasing intracellular calcium concentration 100-fold (Choice C). The calcium released from the sarcoplasmic reticulum diffuses through the myofilament network and binds to troponin C (Choice D). Tropomyosin is then moved out of the way so that actin and myosin can interact, leading to muscle contraction. The final stage of excitation-contraction coupling is myocyte relaxation, which occurs subsequent to calcium efflux from the cytoplasm. Intracellular calcium is removed primarily via an Na⁺/Ca²⁺ exchange pump (NCX) and sarcoplasmic reticulum Ca²⁺-ATPase pump (SERCA). NCX uses the large extracellular Na⁺ concentration gradient to help pump Ca²⁺ out of the cell and, in the process, removes one intracellular Ca²⁺ in exchange for 3 extracellular Na⁺ ions. In contrast, SERCA is a Ca²⁺-ATPase pump that actively transfers Ca²⁺ from the cytosol to the lumen of sarcoplasmic reticulum at the expense of ATP hydrolysis. (Choice A) Calmodulin (calcium modulated protein) is a calcium-binding messenger protein that is present in all cells and mediates many of the regulatory effects of Ca²⁺. Calmodulin is important for excitation-contraction coupling in smooth muscle cells, which lack troponin, unlike cardiac and skeletal muscles. In cardiac muscle, calmodulin is not directly involved in excitation-contraction coupling; rather, it helps regulate intracellular calcium activity and transcription factor signaling. Educational objective: Calcium efflux from cardiac cells prior to relaxation is primarily mediated via an Na⁺/Ca²⁺ exchange pump and sarcoplasmic reticulum Ca²⁺-ATPase pump. __________ References: The therapeutic potential of new insights into myocardial excitation-contraction coupling. (http://www.ncbi.nlm.nih.gov/pubmed/12639859)

A 44-Year-Old Man with Progressive Dyspnea Is Diagnosed with Dilated