Neuromuscular Diseases

The motor unit has four components: a motor neuron in the brain or spinal cord, its axon and related axons that comprise the peripheral nerve, the neuromuscular junction, and all the muscle fibers activated by the neuron. Like other cells, nerve and muscle cells have an external membrane that separates the inner fluids from those on the outside. The fluid on the inside is rich in potassium (K), magnesium (Mg), and phosphorus (P), whereas the fluid on the outside contains sodium (Na), calcium (Ca), and chloride (Cl). When all is quiet, the internal chemical composition of both nerve and muscle cells is remarkably constant and is called resting membrane potential. A primary reason for this constancy lies in the cells' ability to regulate the flow of sodium—thanks to an enzyme in the membrane called Na+/K+ ATP-ase. Because the inside of the cell has less sodium than the outside, there is a negative potential (like a microscopic battery) of 70-90 mV. Under ordinary circumstances, the interior of the cell is 30 times richer in potassium than the extracellular fluid and the sodium concentration is 10-12 times greater on the outside of the cell. At rest, sodium tends to flow into cells and potassium oozes out.

When an impulse or current runs down a nerve and hits a muscle fiber, the action potential of the membrane is suddenly changed; K moves out of the cell and the permeability to Na keeps increasing so that the inside may become positive by as much as 40 mV. In a fraction of a second, however, K moves back again and restores the cell membrane to normal. This process of movement of ions in and out of cells is known as action potential and is the basis for both the transmission of nerve impulses and muscular contractions.

This explains the biochemical processes involved, but anatomy also plays a role in movement. The critical spot is the synaptic cleft, the place where the nerve dips into the muscle. Here, the finely branched nerve fiber inserts into a microscopic bit of muscle tissue, and acetylcholine (ACh), the chemical responsible for the transmission of the nerve impulse, hooks onto the muscle fibers, stimulating them to contract. Enough calcium at the site makes the process go more smoothly, while magnesium slows the process. To keep ACh from accumulating in the cells, the enzyme cholinesterase destroys the excess.

To understand the physiological nature of muscle contractions, it is helpful to examine muscles microscopically. Muscle fibers have an outside membrane called the plasmalemma, an interior structure called a sarcolemma, transverse tubules across the fibers, and an inner network of muscle tissue called sarcoplasma. When a nerve impulse reaches the muscle, an action potential is set up and the current quickly travels in both directions from the motor end plate through the entire length of the muscle fiber. The whole inside of the muscle tissue becomes involved as the current spreads and, aided by calcium, the contractile protein called actin causes the muscle component (myosin) to contract. An enzyme, ATP-ase, helps provide the energy needed for the muscular filaments to slide past each other. Relaxation occurs promptly when Ca flows into the muscle tissue and the cycle is completed. The muscle fiber is now ready to be stimulated again by a nerve impulse.

A constant need for ready energy exists because muscles must be able to respond on demand. Compounds such as creatine, phosphate, adenosine triphosphate (ATP), myoglobin, creatine kinase (CK), calcium, and a host of oxidative enzymes are all involved. Red musculature is usually more efficient than pale muscle because it contains more myoglobin and more oxidative enzymes. In any one motor unit, however, all the muscle fibers are the same type.

Muscles acquire about 90% of the energy they need from glycogen, a starchy compound synthesized and stored in the muscles. A small amount of glucose and some free fatty acids also provide energy both in vigorous exercise and at rest. Many enzymes, too many to name, take part in these energy reactions, and some neuromuscular diseases are caused by a failure of these enzymes to function properly.