Motor end plates

Electron microscopic study reveals an incalculably small space between nerve endings and the effector organ (eg, tlie muscle, cell, or gland) diat is innervated (or controlled) by a nerve fiber. Fbr a nerve impulse to be transmitted from die nerve ending (motor end plate) across die space to die effector organ, a neurohormone is needed. 

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

According to Fig. 6.17 the nerve cell is linked to other excitable, both nerve and muscle, cells by structures called, in the case of other nerve cells, as partners, synapses, and in the case of striated muscle cells, motor end-plates neuromuscular junctions). The impulse, which is originally electric, is transformed into a chemical stimulus and again into an electrical impulse. The opening and closing of ion-selective channels present in these junctions depend on either electric or chemical actions. The substances that are active in the latter case are called neurotransmitters. A very important member of this family is acetylcholine which is transferred to the cell that receives the signal across the postsynaptic membrane or motor endplate through a... 

Motor end-plate or neuromuscular junction = axon terminal in apposition to specialized surface of muscle cell membrane... 

Quantal analysis defines the mechanism of release as exocytosis. Stimulation of the motor neuron causes a large depolarization of the motor end plate. In 1952, Fatt and Katz [11] observed that spontaneous potentials of approximately 1 mV occur at the motor endplate. Each individual potential change has a time course similar to the much larger evoked response of the muscle membrane that results from electrical stimulation of the motor nerve. These small spontaneous potentials were therefore called... 

Bums, B.D. and Paton, W.D.M. (1951). Depolarization of the motor end-plate by decametho-nium and acetylcholine. J. Physiol. (London) 115 41-73. 

At the neuromuscular junction, the terminus of the axon is separated from the sarcolemma by a cleft about 4 nm wide. When an action potential arrives at the terminus, it activates a voltage-sensitive Ca " ion channel. This results in Ca + ions diffusing into the terminus increasing the intracellular Ca + ion concentration, which stimulates exo-cytosis of acetylcholine from the terminus into the cleft. The acetylcholine diffuses across the cleft and binds to receptors on the motor end-plate (Figure 13.12) on the muscle side of the cleft. The binding of acetylcholine to... 

Myasthenia gravis is an autoimmune disease in which antibodies are present in blood and bind to the acetylcholine receptor on the motor end-plate. This prevents the muscles from contracting so that, due to lack of use, they become weak and fatigue easily. In particular, there is difficulty in speaking, swallowing and chewing food. 

Figure 13.12 motor end-plate. The axon terminates very close to the muscle. They are separated by a small gap (the synaptic cleft). When the nerve is stimulated, acetylcholine is released into the cleft where it diffuses across the cleft, and then binds to receptors located on the muscle side of the cleft and initiates an action potential along the sarcolemma. 

Most of the experimental evidence came initially from studies of the frog motor end-plate, where it was shown that the desensitization of the nicotinic receptor caused by continuous short pulses of acetylcholine was associated with a slow-conformational change in that the ion channel remained closed despite the fact that the transmitter was bound to the receptor surface. 

Acetylcholine (ACh) as a transmitter. ACh serves as mediator at terminals of all postganglionic parasympathetic fibers, in addition to fulfilling its transmitter role at ganglionic synapses within both the sympathetic and parasympathetic divisions and the motor end-plates on striated muscle. However, different types of receptors are present at these synaptic junctions ... 

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). 

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. 

Myasthenia gravis is an autoimmune disease resulting from production of autoantibodies against AChR at the motor end plate, causing defects in neuromuscular transmission. Depending on the muscles affected a patient may develop dysphagia or respiratory failure [1]. The appearance of pathological forms of erythrocytes such as stomatocytes, echinocytes etc., in peripheral blood causes microcirculation disorders [2]. 

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. 

Edrophonium is also used to assess the adequacy of treatment with the longer-acting cholinesterase inhibitors in patients with myasthenia gravis. If excessive amounts of cholinesterase inhibitor have been used, patients may become paradoxically weak because of nicotinic depolarizing blockade of the 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. 

The extremely short duration of action of succinylcholine (5-10 minutes) is due to its rapid hydrolysis by butyrylcholinesterase and pseudocholinesterase in the liver and plasma, respectively. Plasma cholinesterase metabolism is the predominant pathway for succinylcholine elimination. Since succinylcholine is more rapidly metabolized than mivacurium, its duration of action is shorter than that of mivacurium (Table 27-1). The primary metabolite of succinylcholine, succinylmonocholine, is rapidly broken down to succinic acid and choline. Because plasma cholinesterase has an enormous capacity to hydrolyze succinylcholine, only a small percentage of the original intravenous dose ever reaches the neuromuscular junction. In addition, as there is little if any plasma cholinesterase at the motor end plate, a succinylcholine-induced blockade is terminated by its diffusion away from the end plate into extracellular fluid. Therefore, the circulating levels of plasma cholinesterase influence the duration of action of succinylcholine by determining the amount of the drug that reaches the motor end plate. 

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... 

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). 

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