Skeletal muscle motor end plate

The somatic motor nervous system or voluntary nervous system consists of nerve libers that irmervate skeletal muscle motor end-plates. 

The action of acetylcholine at the skeletal muscle motor end plate resembles that produced by nicotine. Thus, the choUnoreceptor on skeletal muscle is a nicotinic receptor. Based on antagonist selectivity, however, the autonomic and somatic nicotinic receptors are not pharmacologically identical (see Chapter 14). 

Most of the direct organ system effects of muscarinic cholinoceptor stimulants are readily predicted from a knowledge of the effects of parasympathetic nerve stimulation (see Table 6-3) and the distribution of muscarinic receptors. Effects of a typical agent such as acetylcholine are listed in Table 7-3. The effects of nicotinic agonists are similarly predictable from a knowledge of the physiology of the autonomic ganglia and skeletal muscle motor end plate. 

The neuromuscular junction consists of a motor nerve terminal and skeletal muscle motor end plate, separated by a synaptic cleft that is filled with extracellular fluid (Figure 26.2). 

Nm—Nicotinic receptors are located on the skeletal muscle motor end plate innervated by somatic motor nerves. 

Mecfianism of Action A cinchona alkaloid that relaxes skeletal muscle by increasing the refractory period, decreasing excitability of motor end plates (curare-like), and affecting distribution of calcium with muscle fiber. Antimalaria Depresses oxygen uptake, carbohydrate metabolism, elevates pH in intracellular organelles of parasites. Therapeutic Effect Relaxes skeletal muscle produces parasite death. Pharmacokinetics Rapidly absorbed mainly from upper small intestine. Protein binding 70%-95%. Metabolized in liver. Excreted in feces, saliva, and urine. Half-life 8-14 hr (adults), 6-12 hr (children). 

At the neuromuscular junction, it produces the contraction of skeletal muscle by its direct action and by inactivation of anticholinesterase and has got anticurare action. By virtue of its structural similarity to acetylcholine, it acts as partial agonist on motor end plate. 

Skeletal muscle relaxation and paralysis can occur from interruption of function at several sites along the pathway from the central nervous system (CNS) to myelinated somatic nerves, unmyelinated motor nerve terminals, nicotinic acetylcholine receptors, the motor end plate, the muscle membrane, and the intracellular muscular contractile apparatus itself. 

As indicated earlier, the relaxant effects of the toxin are likewise temporary, and these effects typically diminish within 2 to 3 months after injection.91 The effects apparently wear off because a new presynaptic terminal sprouts from the axon that contains the originally affected presynaptic terminal. This new terminal grows downward, reattaching to the skeletal muscle and creating a new motor end plate with a new source of acetylcholine. The effects of the previous injection are overcome when this new presynaptic terminal begins to function. Another injection will be needed to block the release from this new presynaptic terminal, thus allowing another 2 to 3 months of antispasticity effects. This fact raises the question of how... 

Motor end plate in skeletal muscle ACh Nicotine d-Tubocurarine ... 

Many of the physiological effects of anti-ChEs are attributable to excess neurotransmitter ACh (Taylor 1996). The precise symptoms and the time course depend on the chemicals and the localization of the receptors affected. Early symptoms of cholinergic poisoning represent stimulation of muscarinic neuro-effectors of the parasympathetic system. Effects include slowing of the heart (bradycardia), constriction of the pupil of the eye, diarrhea, urination, lacrimation, and salivation. Actions at nicotinic skeletal neuromuscular junctions (motor end plates) result in muscle fasciculation (disorganized twitching) and, at higher doses. 

Quaternlzation of these alkaloids removes much of their ability to penetrate into the central nervous system and to affect its functions. However, the same variation in chemical structure Increases the Weak ability of these materials to interfere with the action of acetylcholine at the motor end plates of skeletal muscles. 

The depolarization of the motor end-plate receptors produced by suxamethonium (either directly or via repetitive discharge generation by the motor nerve terminals) (40) results in generalized and desynchronized contraction of skeletal muscle fibers. These fasciculations result in aching muscle pain (in up to 90% of patients), most commonly in the neck, pectoral region, shoulders, and back. The pain is most often experienced the day after operation and is worse in ambulatory patients. It is more common in women than in men. Children, elderly patients, athletes, and pregnant women (41) complain less often. Africans also seem to be less susceptible (42). 

Methocarbamol is an aromatic glycerol ether that is a close chemical relative to mephenesin carbamate. Methocarbamol is approved in the USA for parenteral administration to horses as an adjunct to the treatment of acute inflammatory and traumatic conditions of the skeletal muscles and to reduce muscular spasm. Its mechanism of action has not been established, but it may act by central nervous system depression. It has no direct action on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber (Plumb... 

Agents that block the transmission of ACh at the motor end plate are called neuromuscular blocking agents. The therapeutic use of these compounds is primarily as adjuvants in surgical anesthesia to obtain relaxation of skeletal muscle. They also are used in various orthopedic procedures, such as alignment of fractures and correction of dislocations. 

Duchen, L.W. 1971. An electron microscopic study of the changes induced by botulinum toxin in the motor end-plates of slow and fast skeletal muscle fibres of the mouse. J. Neurol. Sci. 14 47-60. 

FIGURE 12 Botulinum toxin causes skeletal muscle paralysis by binding to acetylcholine receptors on the motor end plate. 

Action on Skeletal Muscle Quinine increases the tension response to a single maximal stimulus delivered to muscle, but it also increases the refractory period of muscle so that the response to tetanic stimulation is diminished. The excitability of the motor end-plate region decreases so that responses to repetitive stimulation and to acetylcholine are reduced. Thus, quinine can antagonize the actions of physostigmine on skeletal muscle. Quinine also may produce respiratory distress and dysphagia in patients with myasthenia gravis. 

Similar changes take place in the development of skeletal muscle, but the ability to contract appears somewhat later. In the chick embryo, the first contractions, localized in the muscles of the head and neck, appear at 3 -4 days of development, but distal leg muscles do not begin to contract until 7i days, and distinct motor end plates do not appear until day 13 or 14 (Hamburger, 1968). 

Important toxins are cobramine A and B from cobra toxin and crotactine and crotamine from crotox-in, the toxin of the North American rattlesnake. The toxic proteins are classified according to their mode of action cardiotoxins, neuFotoxins and protease inhibitors (with inhibitory activity toward chymotrypsin and trypsin). Cardiotoxins (heart muscle poisons) cause an irreversible depolarization of the cell membranes of heart muscle and nerve cells. Neurotoxins (nerve poisons) show curare-like activity they prevent neuromuscular transmission by blocking the receptors for the transmitters at the synapses of autonomic nerve endings and at the motor end plate of skeletal muscle. Protease inhibitors inhibit acetylcholine esterase and similar enzymes involved in nerve transmission. 

Andersson-Cedergen, E. Ultrastructure of motor end plate and sarcoplasmic components of mouse skeletal muscle fiber as revealed by three-dimensional reconstructions from serial sections. J. Ultrastruct. Res., Suppl. 1, 1-191 (1959)... 

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