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OBJECTIVES

OBJECTIVES

After studying this chapter, you should be able to:

  • Describe the differences between actin-based and myosin-based regulation of muscle contraction.

  • Outline the composition and organization of the thick and thin filaments in striated muscle tissues.

  • Describe the pivotal role of Ca2+ in the initiation of both contraction and relaxation in muscle.

  • List the various channels, pumps, and exchangers involved in regulating intracellular Ca2+ levels in various types of muscle.

  • List the major energy sources for regenerating ATP in muscle tissue.

  • Identify the preferred energy sources for fast and slow twitch fibers.

  • Understand the molecular bases of malignant hyperthermia, Duchenne and Becker muscular dystrophies, and inherited cardiomyopathies.

  • Explain how nitric oxide (NO) induces relaxation of vascular smooth muscle.

  • Know the general structures and functions of the major components of the cytoskeleton, namely microfilaments, microtubules, and intermediate filaments.

  • Explain the role of mutations in the gene encoding lamin A and lamin in Hutchinson-Gilford progeria syndrome (progeria).

BIOMEDICAL IMPORTANCE

The shape, integrity, and internal organization of all mammalian cells is maintained by an internal network of polymeric protein fibers and associated molecular motors called the cytoskeleton. This structural and mechanical network mediates motional processes such as cytokinesis, endocytosis, exocytosis, secretion, phagocytosis, and diapedesis. Several pathogenic microorganisms, among them Yersinia, Salmonella enterica, Listeria monocytogenes, and Shigella attack or co-opt the cytoskeleton of the infected host as an integral part of their mechanisms of virulence.

Highly specialized muscle cells elaborate extensive internal networks consisting of physically juxtaposed actin and myosin polymers, or fibrils, that form the core of their contractile apparatus. This mechanically powerful contractile machinery is controlled by signal transduction pathways in which the second messenger Ca2+ plays a pivotal role. Muscle tissue is subject to a variety of pathologic conditions, many of them hereditary in nature, including Duchenne-type muscular dystrophy; malignant hyperthermia, a serious complication for some patients undergoing certain types of anesthesia, and cardiomyopathies. Heart failure is a very common medical condition, with a variety of causes. Its rational therapy requires understanding of the biochemistry of heart muscle. For example, many widely used vasodilators—such as nitroglycerin, used in the treatment of angina pectoris—act by increasing the formation of NO.

MUSCLE IS A STRUCTURALLY AND FUNCTIONALLY SPECIALIZED TISSUE

Three Types of Muscle Exist: Skeletal, Cardiac, and Smooth

Muscle is a highly specialized tissue configured to convert the chemical energy of ATP potential into mechanical energy on a mass, macroscopic scale. Three types of muscle are found in vertebrates. Skeletal and cardiac muscle display a striated appearance, a consequence of the parallel alignment of the fibrils of their contractile apparatus. Smooth muscle is devoid of striations, a consequence of the (more) random orientation of its contractile fibrils. Mechanically, these differences in orientation mean that cardiac and skeletal muscle contract and exert force in only ...

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