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The clinical suspicion of neuromuscular disease, disclosed by any of the symptoms or syndromes in the succeeding chapters, finds ready confirmation in the laboratory. The intelligent selection of ancillary examinations requires some knowledge of the biochemistry and physiology of muscle fiber contraction, nerve action potentials, and neuromuscular conduction. These basic subjects, with the relevant anatomy, serve as an introduction to the descriptions of the laboratory methods and the subject matter of the chapters on the diseases of muscle and nerve that follow.

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It is not possible here to review all the biochemical and biophysical data that explain nerve impulse generation and conduction. Since the early studies of Hodgkin (1951) and of Hodgkin and Huxley (1952), tomes have been written on these subjects. Suffice it to say that the nerve and muscle fibers, like other bodily cells, maintain a fluid internal environment that is distinctly different from the external or interstitial medium. The main intracellular constituents are potassium (K), magnesium (Mg), and phosphorus (P), whereas those outside the cell are sodium (Na), calcium (Ca), and chloride (Cl). In both nerve and muscle the intracellular concentrations of these ions are held within a narrow range by electrical and chemical forces, which maintain the membranes in electrochemical equilibrium (resting membrane potential). These forces are the result of selective permeability of the membranes to various ions and the continuous expulsion of intracellular Na through special channels by a pump mechanism (the sodium pump). The function of the sodium pump is dependent on the enzyme Na-K-ATPase (adenosine triphosphatase), which is localized in the membranes.

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This resting membrane potential is therefore the result of the differential concentrations of K and Na. The interior of the cell is some 30 times richer in K than the extracellular fluid, and the concentration of Na is 10 to 12 times greater in the extracellular fluid. In the resting state, the chemical forces that promote diffusion of K ions out of the cell (down their concentration gradient) are counterbalanced by electrical forces (the internal negativity opposes further diffusion of K to the exterior of the cell). At the resting potential, the situation of Na ions is the opposite; they tend to diffuse into the cell, both because of their concentration gradient and because of the relative negativity inside the cell. Because the resting membrane is less permeable to Na than to K, the amount of K leaving the cell exceeds the amount of Na entering the cell, thus creating the difference in electrical charge across the membrane. This discrepancy, in association with the actions of an electrogenic Na:K pump and the presence of impermeant, negatively charged intracellular proteins, creates an electrical potential across the membrane such that, in the resting state, the intracellular compartment is 70 to 90 mV negative (the resting membrane potential).

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From this resting point, any electrical discharge of neural and muscular tissue is predicated on a special property of excitable membranes; ...

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