Structure and Function of Skeletal Muscle

Introduction

In understanding the molecular mechanisms underlying skeletal muscle function, it is easy to lose sight of the forest for the trees. As you learn about each part of the picture, try to keep in mind the whole picture.

• Muscle cells are excited by somatic efferent neurons.
• Muscle cell excitation (the muscle cell action potential) triggers muscle cell activity (contraction).
• Calcium (Ca⁺⁺) is the second messenger that links excitation to contraction.

The organization of the web pages follows that of lectures: we start with an explanation of cross-bridge cycling, which is the molecular basis for movement and force generation by muscle cells. Then we work backwards, describing how Ca⁺⁺ regulates cross-bridge cycling, how excitation regulates intracellular Ca⁺⁺ levels, and finally how the nervous system activates muscle cells. The links are to illustrations from The Molecular Biology of the Cell, a book that is available online through the National Center for Biotechnology Information (NCBI) bookshelf. Each figure link will open as a new browser window, so that you can toggle between text and figures.

For off-campus access, you need to log-in with your UW Net ID via the Healthlinks web page.  Click the link in the upper right-hand corner of the page ("off-campus access (log-in)" inside a red box).  Once logged in, you can access the figures that are available through the NCBI bookshelf.

Book used:

The Molecular Biology of the Cell, 4th^th edition, © 2002 by Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter

Link to NCBI Bookshelf

Skeletal Muscle Structure

To understand how muscle cells achieve work, one first needs to know something about the structure of muscle cells. Skeletal muscle cells, also referred to as muscle fibers (figure 16-68), are large, multinucleate cells that form by the fusion of precursor cells known as myoblasts (figure 22-41) . Within each muscle fiber there are tubes of regularly arranged contractile proteins known as myofibrils (figure 16-69). The striated appearance of skeletal muscle (and cardiac muscle) is due to the alignment of myofibrils within the muscle fiber.

Panel C in figure 16-69 is a diagram of the sarcomere, which is the functional unit of the myofibril. Each sarcomere contains thick filaments (green) and thin filaments (red), which are anchored to the Z-disc (blue). The thin filament is made up of actin, and the regulatory proteins tropomyosin and troponin. The thick filament is made up of the protein myosin. Myosin molecules consist of two globular heads with a long tail (figure 16-51).  Myosin molecules are arranged in the thick filament so that the tails point inward toward the center of the sarcomere, and the heads decorate the outer ends of each thick filament (figure 16-72). The myosin heads are known as cross-bridges because they can bind to and move along actin in the thin filament. It is this actin-myosin interaction that is the molecular basis for force generation and movement in muscle cells.

When muscle cells contract, the thick and thin filaments do not change their size. Instead, the interaction between the myosin heads and actin pulls the thin filaments past the thick filaments. This is known as the sliding filament mechanism.

Cross-bridge Cycling

As stated above, cross-bridge cycling forms the basis for movement and force production in muscle cells. Each cycle of myosin binding to actin and movement of the thin filament involves the hydrolysis of one ATP molecule. Figure 16-58 outlines the specific steps involved.

This figure starts the cycle with a myosin cross-bridge attached to actin. ATP binding causes the dissociation of myosin from actin. In the absence of ATP (as occurs after death), myosin cannot dissociate from actin, and the muscles become stiff. This is known as rigor mortis. The state where the low-energy myosin head is bound to actin is known as the rigor configuration.

ATP hydrolysis causes a shape change so that the myosin head is cocked. The products of ATP hydrolysis (ADP and inorganic phosphate) remain bound. Cocking of the myosin head puts it in line with a new binding site on the actin filament.

Myosin binds to actin and the powerstroke occurs. Initial weak binding releases inorganic phosphate. Stronger binding triggers the powerstroke and the release of ADP. The powerstroke involves the return of the myosin head to its low-energy conformation. The powerstroke generates force, pulling the thin filament toward the center of the sarcomere. Binding of another ATP molecule causes dissociation of myosin from actin and the cycle repeats itself.

Keep in mind that the cross-bridges cycle independently from one another--at any given time, some cross-bridges will be bound in the rigor configuration, some will be undergoing the powerstroke, and some will be unbound. Because many cross-bridges cycle independently, muscle contraction is smooth, not ratchet-like.

Note that the tension (the amount of force produced by the muscle) is going to depend on the proportion of cross-bridges that are active (i.e. can bind to actin). As described in the next section, this depends upon the concentration of Ca⁺⁺ in the muscle cell cytoplasm. Another factor that influences the proportion of active cross-bridges is the initial length of the contracting muscle (the Length-Tension relationship).

CALCIUM REGULATION OF CONTRACTION