Disorders of Muscle Excitability

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Disorders of Muscle Excitability Chapter 44 Disorders of Muscle Excitability Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

FIGURE 44-1: Motor endplates from rabbit intercostal muscle stained with Löwit’s gold chloride method. a, terminal axonal arborization; b, nucleus; d, region where the myelin sheath ends; n, neural branch. (From Ramón y Cajal, S. Textura del sistema nervioso del hombre y los vertebrados. Madrid: N. Moya, 1899.) Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

FIGURE 44-2: Photomicrograph of the human neuromuscular junction FIGURE 44-2: Photomicrograph of the human neuromuscular junction. In normal muscle, Ach receptors are associated with the terminal expansions of the junctional folds and the architecture of the postjunctional membrane follows closely the distribution of active zones in the presynaptic membrane. b, basal lamina; I, infoldings; m, mitochondria; M, myocyte; N, nerve terminal; r, ribosomes; s, synaptic space; S, Schwann cell. Courtesy of A. Engel. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

FIGURE 44-3: Schematic representation of the key synaptic elements of the neuromuscular junction. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

FIGURE 44-4: Cellular and molecular organization of the skeletal myocyte. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

FIGURE 44-5: Myofibrillar apparatus and muscular contraction FIGURE 44-5: Myofibrillar apparatus and muscular contraction. Troponin is essential in Ca2 regulation of contraction and is represented as a small, boomerang-shaped trimer. It consists of three subunits (TnT (yellow), TnC (red) and TnI (cyan)) and, together with tropomyosin (drawn as a helicoidal dimeric string), is located in apposition to the actin filament (represented as an orange-yellow helical chain with its myosin binding sites in blue). Myosin filament heads, represented in the lower part of each panel, possesses ATPase activity. Redrawn from Takeda, S. et al. Structure of the core domain of human cardiac troponin in the Ca2+-saturated form, Nature 424: 35–41 and Brown J. H. et al. Deciphering the design of the tropomyosin molecule, PNAS 98: 8496–8501, 2001. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

FIGURE 44-6: Molecular physiology of muscle excitation–contraction coupling. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

TABLE 44-1: Disorders of Muscle Excitability Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.

FIGURE 44-7: Block of the acetylcholine receptor in myasthenia gravis FIGURE 44-7: Block of the acetylcholine receptor in myasthenia gravis. Compound muscle action potentials recorded from the abductor digiti minimi of human subjects during repetitive stimulation of the ulnar nerve at three stimuli per second. (A) A recording from a normal individual shows no change in the amplitude of the muscle electrical response during the stimulation interval. (B) In a patient with myasthenia gravis, the same stimuli produce a 40% decrement in response amplitude over the first five stimuli, with a slow partial recovery during subsequent stimulation. Similar studies from a patient with severe myasthenia gravis before (C) and 2 minutes after (D) intravenous administration of 10 mg edrophonium, a short-acting acetylcholinesterase inhibitor. Note the change in amplitude scale between the two recordings and the reversal of the abnormal decrement by edrophonium. Copyright © 2012, American Society for Neurochemistry. Published by Elsevier Inc. All rights reserved.