1. Vertebrate skeletal muscle is comprised of long, parallel cells, called fibers, which run from tendon (attached to bone) to tendon. Within these cells, bundles of thick and thin fibers, the contractile protein machinery of muscle, are wrapped in sarcoplasmic reticulum. These bundles are called myofibrils. (fig. 17-29, Lodish).

2. Lengthwise, each myofibril consists of a repeating structure called the sarcomere. Sarcomeres contain the actin thin filaments, attached to the Z-lines or Z disks, as they may be more accurately called. (Z for zig-zag, although the surface of the Z-disk is more like a waffle pattern.) The interior waffle-like structure of the Z-disks contains a lot of the protein alpha-actinin, which is also used to connect microfilaments to proteins on the plasma membrane, whereas the periphery of the Z-disks has desmin attached. Desmin is one of the molecules used to "glue" various types of cells together to keep tissues intact. You should know about the location and function of alpha-actinin and desmin. Look here for a classic article on localization of desmin and alpha-actinin.

3. The sarcomere is complex, with additional proteins such as CapZ, tropomodulin, and titin. (fig. 17-31, Lodish)

3. Contraction of skeletal (and heart) muscle occurs when the myosin thick filaments slide relative to the actin thin filaments, thus shortening the length of a sarcomere. (fig. 17-30, Lodish)

4. Myosin ATPase produces contractile force from the energy released from ATP hydrolysis.

• ATP binding to myosin causes release of the myosin "head" from actin. After release, the energy from ATP hydrolysis is stored in the myosin and released to cause contraction when myosin again comes in contact with actin.

• Myosin kinetics and the previous diagram help us to understand the cycle of active contraction, the relaxed state, and the development of rigor: (A = Actin, M = Myosin, P = Phosphate. AM = Actomyosin, Myosin with its head region attached to Actin. AM*ATP = Myosin with ATP attached, bound to Actin.) (Make sure you compare the cycle of Myosin activity in relaxed and in contracting muscle. Play particular attention to the rate limiting reactions and the release of ADP and Phosphate. What condition results in rigor?) Notice that the presence of a long-lived enzyme-product complex (myosin-ADP-phosphate) shows us that the kinetics can be more complicated than Michaelis-Menten theory predicts.

5. The coupling of electrical excitation and contraction is the result of Ca⁺⁺ release from the lumen of the sarcoplasmic reticulum when a depolarization passes into the muscle cell interior via the T-tubules. An action potential traveling along the external cell membrane follows the cell membrane into the T-tubules and deep into the muscle cell interior.

• The T-tubules end in sacs which lie next to the membranes at the ends of sacs of sarcoplasmic reticulum. (fig. 17-32a, Lodish), (fig. 17-32b, Lodish) Ca⁺⁺ channels are opened in response to depolarization and Ca⁺⁺ flows into the cytosol, where the actin and myosin are located. Ca⁺⁺ concentrations in the cytosol rise from 10^-8 or 10^-7M to about 10^-6M. Active transport pumps transport Ca⁺⁺ back into the lumen of the sarcoplasmic reticulum so that when Ca⁺⁺ is no longer being released, cytosol concentrations of Ca⁺⁺ drop back to resting levels. Another diagram makes clearer the relationships between the T-tubules and the sarcoplasmic reticulum:
  

• Ca⁺⁺ activates muscle by 2 Ca⁺⁺ ions binding to each Troponin-C (TN-C) unit. A conformational change in troponin causes the TN-I subuit to release from the actin filament, resulting in tropomyosin sliding deeper into the grooves in the actin helix and uncovering binding sites for myosin on actin. (fig. 17-33, Lodish)

6. Low ATP concentrations within myofibrils cause rigor (RYE-GORE). Therefore, vertebrate skeletal muscle has several mechanisms which result in keeping ATP at suitable concentrations, even under adverse circumstances.

• Myoglobin in the muscle cells provides a temporary source of oxygen and releases it when blood oxygen pressures become low.

• Fermentation, producing Lactic Acid, permits muscle cells to make a little ATP even if there is no oxygen available in the muscle cells.

• The Lohman reaction provides a buffer against heavy demand for ATP lowering ATP concentrations in the myofibrils. ATP produced by the mitochondria, usually located in the periphery of the cell, is used to phosphorylate creatine to make creatine phosphate. The creatine phosphate diffuses into the myofibrils, where it is used to phosphorylate ADP to ATP, as needed.

All text and images, not attributed to others, including course examinations and sample questions, are Copyright, 2007, Thomas J. Herbert and may not be used for any commercial purpose without the express written permission of Thomas J. Herbert.