Biochemical Strategies for Ultrarunning—Draft Version
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Written by Bruce R. Copeland, PhD   
Wednesday, 14 May 2008 15:49
Article Index
Biochemical Strategies for Ultrarunning—Draft
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Appendix A: The Biochemistry of Muscle Contraction
Appendix B: The Biochemistry of Nerve Signaling
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Appendix A: The Biochemistry of Muscle Contraction

Our skeletal muscles are bundles of long, parallel muscle cells. Each muscle cell contains a repeating network of thin filaments of actin protein and thick filaments of myosin protein oriented along the length of the cell. These thin and thick filaments overlap and can slide partially past each other. The myosin proteins in the thick filaments have the capability to bind to and move along adjacent actin fibers, consuming cellular ATP as they pull their way along the actin thin fibers [Webb, MR, and Trentham, DR. Chemical mechanism of myosin-catalyzed ATP hydrolysis. In: Peachy, L.D., Adrian, R.H., and Geiger, S.R., ed. Handbook of Physiology. Bethesda, MD: American Physiological Society.1983;237-255]. The binding of myosin to actin is regulated by tropomyosin and troponin proteins that are associated with actin thin filaments. Under relaxed or elongated conditions, the tropomyosin prevents myosin binding, and the thick filaments therefore slide freely along the thin filaments.

Muscle contraction is initiated when all the cells in the bundle (simultaneously) receive a signal from their motor nerve in the form of an action potential (see Appendix B: The Biochemistry of Nerve Signaling). The action potential is a transient electrical polarization of the cell membrane that is propagated to a region of the cell membrane where there is a special connection (T tubule) to the sarcoplasmic reticulum. The sarcoplasmic reticulum is an organelle in the interior of the muscle cell that sequesters (accumulates) calcium ions. When the sarcoplasmic reticulum is stimulated by the action potential, it releases large amounts of calcium ions into the cytoplasm. This spike of cytoplasmic calcium ions causes a conformational change in the troponin and tropomyosin proteins that are associated with actin thin filaments. As a result of this conformational change, the myosin in thick filaments can bind to actin and use cellular ATP to pull its way (ratchet fashion) along its nearby actin thin filament, thereby contracting the length of the muscle cell.

As soon as the sarcoplasmic reticulum has released its calcium contents, and the action potential has dissipated, the sarcoplasmic reticulum begins pumping calcium ions back into its interior from the cytoplasm. It consumes ATP for this pumping process—although not anywhere near as much ATP as is used by myosin for muscle cell contraction. By the time the muscle cell has completed its contraction, the cytoplasmic calcium concentration has dropped to normal levels, and troponin and tropomyosin have converted back to their normal conformation. This prevents binding of thick filaments to thin filaments and allows the muscle cell to relax back to its normal length (i.e., to elongate).

Muscle cells require large amounts of ATP. Mitochondria are cellular organelles, which specialize in the production of ATP under aerobic conditions. Ideally, muscle cells have large quantities of carbohydrate, typically in the form of glycogen. As needed, glycogen is converted into three-carbon sugars in the cytoplasm by way of the citric acid cycle, which produces small amounts of ATP. The three-carbon sugars are then consumed by the mitochondria to produce much larger quantities of ATP. Since, the muscle cell uses so much ATP for each contraction cycle, it stores some of the ATP energy in its cytoplasm in the form of creatine phosphate, which can be easily and quickly converted back into ATP.

There are several different types and classifications of skeletal muscle cells that are specialized for different muscular activity. Type I (slow twitch) muscle cells make up the classical aerobic red muscle that carries out high-endurance, slower and lower-force contraction. These are the primary muscle cells used for distance running, distance cycling, hiking, etc., and they contain large amounts of oxygenated myoglobin (which produces the red color of aerobic muscle), large stores of glycogen, and large numbers of mitochondria. Type II (fast twitch) muscle cells come in several variations, but all carry out faster and more forceful contraction than Type I muscle cells. Type II muscle cells have a larger cross section than Type I muscle cells and contain considerably less myoglobin, considerably fewer mitochondria, and considerably more creatine phosphate. These are the muscle cells used for sprinting and lifting big weights, but distance runners need some Type II muscle for running up shorter hills, etc. The prototypic Type II muscle is white and is called fatigable. There are also intermediate fatigable and fatigue resistant Type II muscle cells that, respectively, have more Type I character than fatigable Type II cells. Although we each have some individual genetic predisposition to produce more or less Type I or Type II muscle, individual muscle cells can actually interconvert between types over time, depending on whether we do a lot of resistance training or aerobic exercise with a particular muscle.

Quite a variety of things can go wrong—some easily repairable, some not. Muscle cells, like nerve cells, require appropriate amounts of potassium and sodium ions to produce action potentials, (see Appendix B: The Biochemistry of Nerve Signalling). Muscle cells also require significant quantities of calcium ions. If quantities of any of these ions get too far out of balance, the cell may generate action potentials or calcium signal spikes that have the wrong magnitude, duration, or propagation. This typically causes the cell to waste ATP in various ways. When muscle cells use up their carbohydrate reserves, their mitochondria cannot produce enough ATP, and contraction does not occur. The muscle cell is said to be fatigued. A worse situation occurs if ATP runs out during a muscle contraction or if too much calcium is released into the cytoplasm from failing mitochondria. Under these conditions the muscle cell becomes locked in a contracted state. This leads to muscle soreness and tightness. If enough muscle cells reach this state simultaneously, a muscle cramp occurs. Muscle cell carbohydrate reserves can be replenished via the bloodstream (assuming the liver has carbohydrate reserves to transfer into the blood). However, if an aerobic (high oxidative) muscle cell (Type I or Type II fatigue resistant muscle) goes too long without sufficient carbohydrate (tens of minutes), some mitochondria begin to undergo oxidative damage. Cells contain many mitochondria, but producing new mitochondria requires hours to days. If enough mitochondria are damaged, the cell itself begins to experience oxidative damage and becomes programmed for cell death. Synthesis of new muscle cells takes days.

Comments (1) Comments are closed
1 Wednesday, 15 October 2008 15:17
Bruce Copeland
Due to popular demand, I have posted a draft version of this special topics article. References and figures remain to be completed, but the meat of the article is here for those of you who are desperate.

Bruce Copeland