Physiology of Musculoskeletal System

Neuromuscular Junction & Contraction of Smooth Muscle

Dr. Maher D. Fuad Fuad (MBChB, MPH) Lecturer International Medical School Management and Science University

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Transmission of impulses from nerves to skeletal muscle fibers: The neuromuscular junction:
The skeletal muscles are innervated by large myelinated nerve fibers that originated from anterior horns of the spinal cord. As the axon supplying a skeletal muscle fiber approaches its termination, it loses its myelin sheath and divides into a number of branches. Each nerve fiber branches many time to form a complex of branching nerve terminals which invaginates into an invaginated muscle fiber membrane called the synaptic gutter or synaptic trough. The junction between the nerve terminal and the muscle fiber is called the neuromuscular junction which is located at the fiber midpoint so that the actin potential in the muscle fiber travels in both directions.

The space between the terminal and the fiber membrane is called the synaptic cleft which is occupied by spongy reticular fibers called basal lamina through which diffuses ECF. At the bottom of the gutter is the part of the muscle fiber membrane adjoining the nerve terminal called the motor end plate. In the motor end plate are numerous smaller folds of the muscle membrane called subneural clefts, which greatly increase the surface area of motor end plate at which the synaptic excitatory acetylcholine (Ach) transmitter can act. The acetylcholine is synthesized in the cytoplasm of the nerve terminal but is rapidly absorbed into many small synaptic vesicles. Attached to the matrix of the basal lamina are large quantities of the enzyme acetylcholinestrase ,which is capable of destroying acetylcholine. When the action potential arrives at the nerve terminal, this opens many voltage-gated Ca channels at the nerve terminal. As a result, the Ca+2 ion concentration in the terminal
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increase about a hundred-fold, which in turn increases the rate of fusion of the acetylcholine (Ach) vesicles with the terminal membrane by about 1 OOO-fold. As each vesicle fuses, its outer surface ruptures through the cell membrane, thus causing exocytosis of acetylcholine (Ach) into the synaptic cleft. Within about 1 msec after Ach is released by the axon terminal, much of it has already diffused out of the synaptic gutter and no longer acts on the muscle fiber membrane, and all the Ach is destroyed by the acetylcholinestrase in the basal lamina lying between the nerve terminal and the subneural clefts. However, the very short period of time that Ach remains in contact with the muscle fiber membrane is almost always sufficient to excite the muscle fiber. The rapid removal of the Ach prevents re-excitation after the muscle fiber has recovered from the first action potential. During this very short time of Ach release, it interacts with nicotinic acetylcholine receptors that attached to Ach-gated Na+ channels. The interaction of Ach with the receptors causes conformational changes in these transmembrane channel proteins that lead to open the Ach-gated Na channels. These channels allow Na ions to flow though the channels. The sudden inflow of Na ions into the muscle fiber causes the membrane potential in the local area of the muscle fiber to increase in the positive direction, creating a local potential called the end-plate potential. If the summation of many end-plate potentials is sufficient enough, it may initiate the positive feedback effect on voltagegated Na channel activation and a propagated action potential will occurred.

The Smooth muscles

Smooth muscle can generally be divided into two major types: 1. Multiunit smooth muscle: this type is composed of discrete smooth muscle fibers. Each fiber operates entirely independent of the other and is often innervated by a single nerve ending. The nerve terminal secretes acetylcholine or norepinephrine, which cause local depolarization of the membrane and not action potential. This depolarization causes muscle contraction. Therefore, the action of these muscle fibers is controlled mainly by nerve signals and they are not exhibiting spontaneous contraction. Such muscle fibers are the muscle fibers of the ciliary muscle of the eye, the iris of the eye, the pilaerectar muscle that cause erection of the hairs when stimulated by the sympathetic nervous system, and the smooth muscle of many of the large blood vessels. 2. Visceral (unitary) smooth muscle: they are similar to multiunit fibers except that: (A) they are usually arranged in sheets or bundles and the cell membrane contact each other at multiple points to form a gap junctions through which ions can flow freely from one cell to the next. Therefore, the fibers form a functional syncytium that usually contract in large areas at once. When the action potential
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generated in one area of the muscle, it will excites the adjacent fibers without secretion of any transmitter substance, but the electrical current flows through the gap junctions and therefore easily spread directly from one smooth muscle fiber to the next. (B) They are able to generate action potential, (C) The control of some visceral smooth muscle is by non-nervous stimuli and some of them are selfexcitatory. This type of muscle is found in most of the organs of the body especially in the wall of the gut, the bile ducts, the ureters, and uterus.

The difference between smooth muscle and skeletal muscles:

1- Histological differences (already discussed in the first lecture of MSK) 2- Muscle contraction differences: A. The single twitch contraction time of smooth muscle is about 30 times as long as in skeletal muscle. This is due to the slowness of the chemical reactions that cause the contraction. B. Less energy is required to sustain the same tension of contraction in smooth muscle as in skeletal muscle. C. The smooth muscle is able to shorten a far greater percentage of its length than can skeletal muscle. Skeletal muscle has a distance of contraction equal to only 25-30% of its length, while smooth muscle can often contract quite effectively to 50-75% of its stretched length, D. The maximum force of smooth muscle contraction per cm cross-sectional area is greater than the skeletal muscle contraction. E. Smooth muscle contraction can be initiated by nerve impulses or by hormones and other F. Factors. While skeletal muscle contraction cannot be initiated by themselves and only initiated by nervous impulses. G. In smooth muscle, both contraction and relaxation are due to the presence of excitatory and inhibitory receptors at their membranes. The contraction of skeletal muscle is due to activation of excitatory receptors while relaxation is achieved in the absence of inhibitory receptors at the membrane of skeletal muscle fiber. H. Some smooth muscle is self-excitatory, i.e. Rhythmical tissues while the skeletal muscle fiber is not a rhythmical tissue. I. Smooth muscle does not contain troponin. Therefore smooth muscle contraction is activated by an entirely different mechanism. . J. Smooth muscle can maintain a state of long-term steady contraction called smooth muscle tone. In contrast to skeletal muscle tone, tonic contraction of smooth muscle caused mainly by local tissue factors or circulating hormones such as angiotensin, vasopressin, or norepinephrine and to less extent by nervous and action potential stimulating factors.
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3- The membrane potential differences: A. In normal resting state, the membrane potential of smooth muscle is usually about -50 to -6omv, i.e. about 30mv less negative than in skeleta1 muscle. B. The action potentials of visceral smooth muscle occur in two different form: 1. Spike potential as those seen in skeletal muscle. 2. Action potential with plateau in which repolarization is delayed which account for the prolonged periods of contraction that occur in same types of smooth muscle such as in ureter, uterus, cardiac muscle, and in same type of vascular smooth muscle. C. The smooth muscle cell membrane has far more voltage-gated Na-Ca channels and few voltage-gated Na channels than skeletal muscle fiber. Therefore, Na participates little in the generation of the action potential in most smooth muscle. Instead, the flow of Ca ions to the interior of the fiber is mainly responsible for the action potential and the initiation of the smooth muscle contraction. 4- The main source of Ca ions that initiate the contraction process in smooth muscle is from ECF and not from the sarcoplasmic reticulum which may contribute to small extent for the increase in the ICF Ca in some of the smooth muscle.

5- The junction between the nerve terminals and smooth muscles are called diffuse junction while those between the nerve terminal and skeletal muscle fiber is called neuromuscular junction. In the diffuse junction the nerve fiber branch diffusely on top of a sheet of muscle fiber without making a direct contact with smooth muscle fibers. The multiple branches of the nerve fibers are beaded with enlargements (called varicosities) that are neurotransmitter substance released from the nerve fiber is then diffuse into the interstitial fluid and then to the smooth muscle fiber. 6- The neurotransmitter at the neuromuscular junction of skeletal muscle is only acetylcholine; while of smooth muscle is acetylcholine or norepinephrine. 7- Stress-relaxation of smooth muscle: it is the ability of smooth muscle to change length without marked changes in tension, i.e. over a period of time the tension of a stretched muscle will return almost to its original amount.

Dr. Maher D. Fuad Fuad

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