A 55-year-old man comes to the office for follow-up of hypertension and coronary heart disease. He has been on several medications in the past with suboptimal blood pressure control. The physician considers adding verapamil to the patient's current regimen, as its vasodilatory properties make it useful for controlling systemic hypertension. Verapamil also affects cardiac contractility but has a minimal effect on skeletal muscle. Which of the following properties of skeletal muscle is responsible for its resistance to the medication?

Question

A 55-year-old man comes to the office for follow-up of hypertension and coronary heart disease.  He has been on several medications in the past with suboptimal blood pressure control.  The physician considers adding verapamil to the patient's current regimen, as its vasodilatory properties make it useful for controlling systemic hypertension.  Verapamil also affects cardiac contractility but has a minimal effect on skeletal muscle.  Which of the following properties of skeletal muscle is responsible for its resistance to the medication?

Quizplus · Accepted Answer

11ec160b_36c3_4224_9249_abd33c0beab5_MD0001_00 Calcium plays an important role in excitation-contraction coupling in cardiac, smooth, and skeletal muscle cells. Myocyte depolarization causes activation of L-type calcium channels on the plasma membrane. In cardiac and smooth muscle cells, this leads to an influx of extracellular calcium that activates sarcoplasmic RyR channels, inducing the release of additional calcium from the sarcoplasmic reticulum (calcium-induced calcium release). The released calcium binds to troponin (cardiac muscle) or calmodulin (smooth muscle), allowing actin and myosin to interact and cause muscle contraction. In contrast, the L-type calcium channels in skeletal muscle directly interact with RyR calcium channels to release calcium from the sarcoplasmic reticulum. This mechanical coupling between the receptors allows sarcoplasmic calcium release to occur without significant influx of calcium across the plasma membrane. Verapamil is a nondihydropyridine calcium channel blocker that acts by blocking L-type calcium channels, preventing the initial calcium influx into cardiac myocytes and vascular smooth muscle cells. Because skeletal muscle is not dependent on extracellular calcium influx, calcium channel blockers do not affect skeletal muscle contractility. (Choice A) Troponin (but not calmodulin) is responsible for contraction of both cardiac and skeletal muscle. Unlike skeletal muscle, cardiac muscle is affected by verapamil due to its dependence on extracellular calcium to induce calcium release from the sarcoplasmic reticulum. (Choice B) A rise in intracellular calcium concentration results in a structural change in the troponin complex that allows actin and myosin to interact and cause skeletal muscle contraction. Calcium channel blockers do not affect troponin's affinity to intracellular calcium. (Choice C) An elaborate T tubule system is present in skeletal and cardiac muscle but not in smooth muscle. T tubules are a communication of the extracellular space that allows the depolarization impulse to reach deep into the cell, nearer to the myofilaments. They are in close proximity to the sarcoplasmic reticulum and therefore facilitate rapid release of intracellular calcium stores. (Choice D) Unlike cardiac myocytes and specialized smooth muscle tissue (eg, gastrointestinal tract, ureters), skeletal muscle does not display automaticity and contracts only in response to the neurotransmitter acetylcholine. However, the mechanical coupling between L-type and RyR calcium channels is responsible for skeletal muscle's resistance to verapamil. Educational objective: Contraction initiation in cardiac and smooth muscle cells is dependent on extracellular calcium influx through L-type calcium channels, which can be prevented by calcium channel blockers (eg, verapamil). Skeletal muscle is resistant to calcium channel blockers, as calcium release by the sarcoplasmic reticulum is triggered by a mechanical interaction between L-type and RyR calcium channels. __________ References: Role of ryanodine receptor subtypes in initiation and formation of calcium sparks in arterial smooth muscle: comparison with striated muscle. (http://www.ncbi.nlm.nih.gov/pubmed/20029633)

A 55-Year-Old Man Comes to the Office for Follow-Up of Hypertension