THE EXCITATION-CONTRACTION COUPLING PAGE!

Initiation of Muscle Contraction: also known as "Excitation-Contraction Coupling" Troponin and tropomyosin are the "regulatory proteins" of muscle contraction, actin and myosin are the "contractile proteins" of muscle contraction, and titin and nebulin are the structural proteins that hold the actin and myosin in place between the z-disk proteins that separate sarcomeres. Sarcomeres are repeating contractile units within a muscle fiber. The z-disk proteins, seen in side view, are responsible for the appearance of the "z-lines" when skeletal muscle fibers are viewed under a microscope. Excitement of the sarcolemma by an action potential is transmitted to the SR via the T-tubule system. In response to the action potential, "foot proteins," which form Ca 2+ channels in the SR open up and release Ca2+ from the SR into the sarcoplasm surrounding the myofilaments. Ca2+ binds to troponin, associated with the thin filament, and activates the sliding filament mechanism, as described on a previous page, causing muscle contraction. Recall, there were many events in the sliding filament theory! Excitation of the Muscle Cell Membrane at the Neuromuscular Junction (Myoneural Junction) motor units A motor unit (or neuromotor unit) is a somatic motor neuron together with all the individual muscle fibers it innervates. Recall that "somatic" means voluntary! Generally, each muscle fiber (cell) is innervated by a single motor neuron near the center of the muscle fiber. A single motor neuron, however, with numerous axon collaterals and even more numerous axon terminals, may innervate anywhere from a few muscle fibers to several hundred muscle fibers. Small motor units: The fewer muscle cells per motor neuron, the more delicate, fine or controlled the movements possible. In the graphic used here to depict motor units, we see 2 motor units, one with 2 muscle fibers and one with 3 muscle fibers; these would represent very small motor units involved in very delicate movements. Example: The eye muscles have an innervation ratio of about 1 neuron to 3 muscle fibers (1:3). This is logical because the eye muscles must often make rapid, very highly coordinated, or "fine" movements. Large motor units: The more muscle cells per motor neuron, the more crude are the movements possible. In other words we lose "fine control." The advantage of large motor units is that a large muscle composed primarily of very large motor units is capable of performing simple tasks without having to receive tremendous quantities of nerve signals.

Example: Large postural muscles of the back have an innervation ratio of 1:100's (ie. one motor neuron innervates hundreds of muscle fibers). This is logical because the postural muscles must keep performing the same job over extended periods of time; essentially holding the body in the upright position. This requires continuous nervous signals. It is easier to activate just a few nerves continuously rather than many nerves continuously. trophic effects of nerves on muscles Nerve cells not only instruct muscles to contract but also exert trophic effects on muscle cells to help maintain the structural integrity of the muscle. This means that neurotransmitters, and other chemicals released by nerves at the same time that they release neurotransmitter vesicles, help maintain the size and health of muscle cells. This, in turn, means that if the nerve supply to a muscle is disrupted, the muscle will atrophy for two reasons. The muscle would atrophy i) due to reduced use, and ii) due to a reduction in trophic effects of neurotransmitters on the muscle cells. If the nerve supply to a muscle is disrupted for 1-2 years, the muscle generally suffers irreparable damage. myoneural junction (MNJ) = neuromuscular junction (NMJ) The point of contact between a motor neuron and a muscle cell is referred to as the NEUROMUSCULAR JUNCTION (NMJ), or MYONEURAL JUNCTION (MNJ). The NMJ is a synapse between a nerve cell and a muscle cell. The transmitter released by motor nerves at the NMJ is acetylcholine (ACh). ACh released by the nerves binds to specific ACh receptors on the "muscle side" of the synapse. The "muscle side" of the synapse is called the "motor end-plate." There is actually a small gap between the axon terminal of a motor neuron and the motor end plate; the gap is called the synaptic cleft, and transmitters released from the axon terminal must diffuse across the synaptic cleft to reach the motor end plate. The receptors on the motor end plate that respond to ACh are called "cholinergic" receptors. The cholinergic receptors on the motor end-plate of the NMJ are stimulated by ACh, but they can also be stimulated by nicotine, a chemical from tobacco plants. For this reason, the cholinergic receptors at the NMJ are known as "nicotinic cholinergic" receptors. Don't forget about the fact that the NMJ can be stimulated by nicotine. This information will be quite useful when we get to neurophysiology, and of even more use when you study pharmacology! One other interesting aspect of the NMJ is the depth to which the axon terminal of the motor neuron is typically embedded into the muscle tissue. Despite the presence of the synaptic cleft between the axon terminal of a motor nerve and the motor end plate of the muscle fiber, the axon terminal appears to be buried in the surface of the muscle cell (ie. there is a depression in the muscle fiber at the site of the NMJ). This means that nerves are fairly firmly attached to the muscles they innervate; otherwise, nerves might be torn away by the action of the muscles themselves! ACh initiates the sequence of muscle membrane events leading to contraction (excitation-contraction coupling, as described above). Summary of the Events Leading to Contraction

The event that leads to the contraction of a skeletal muscle fiber (cell) is the arrival of nerve impulses (action potentials) at the NMJ. Nerve cells that carry impulses to muscle cells are called motor neurons. The cell body of motor neurons are in the spinal cord or in the brain stem. In other words, the cell body (also known as the perikarya) of a motor nerve is a long way away from the muscle to which it is attached. Motor nerves send a very long cytoplasmic process, called the axon, to the skeletal muscle. Notice that the end of the axon has many "axon terminals." Near the skeletal muscle, the axon may branch into several axon collaterals, which in turn branch to form many axon terminals innervate several, or even several hundred, muscle fibers. 1. Nerve impulses (action potentials) are transmitted to the muscle cells by motor neurons. 2. Action potentials are chemically transmitted to the sarcolemma by the diffusion of ACh across the synapse at the NMJ. 3. As ACh binds to cholinergic receptors on the motor end plate, the cholinergic receptors cause the opening of unique ion channels in the motor end plate which allow a lot of inward Na + diffusion, and a little bit of outward K+ diffusion. The net effect of the inward Na + diffusion is to depolarize the motor end plate (make the muscle cell more positive inside in the region of the motor end plate) and to generate an action potential in the muscle cell when the membrane is sufficiently positively charged to reaches a special potential known as the "threshold potential." 4. The action potentials spread over the muscle cell membranes and continue to be propagated by the T-tubule system. Remember, t-tubules are tubes, formed by invaginations of the muscle cell membrane, that travel deep into the muscle cells, and wrap around all of the myofibrils. 5. Excitement of the T-tubule membranes activates the "foot proteins" (calcium channels) that release Ca 2+ from the SR and into the sarcoplasm surrounding the myofilaments (the thin actin filaments and thick myosin filaments). 6. Ca2+ binds to troponin on the thin filament, moving tropomyosin out of the way so that the contractile proteins, actin and myosin, can interact and begin to shorten the muscle (ie. to contract). 7. In order to relax the muscle, Ca2+ must be actively re-sequestered, against its concentration gradient, by ATP-driven Ca 2+ pumps which push the Ca2+ back into the SR. The SR can recapture all of the Ca2+ released within a small fraction of a second, so muscle contraction ends quickly when we stop sending signals to a muscle.
David Currie. Copyright 2000. All rights reserved. Revised: February 05, 2007