Abstract
Skeletal muscle paralysis is a clinical symptom in many cases of nerve injury or brain hemorrhage and it leads to the atrophy of muscles. The structural, biochemical, physiological and pharmacological changes of the denervated muscle might be the important subject of investigation at present. In this article, the experimental results of my colleagues and other many investigators are summarized in special references to the fundamental finding on the denervated muscle.
The most obvious changes in a denervated muscle are weight loss and decrease in fiber diameter of individual muscle fibers. Weight loss and decrease in fiber diameter initially proceed at a rather rapid rate. After 7 weeks' denervation there is a 20 to 30 per cent weight loss in rat anterior tibial muscle. The nuclei of denervated muscle fiber may alter in shape and staining reaction and appear to increase in number. In the muscles denervated for relatively long periods,35 to 200days, fine structural changes in cell membrane were observed. Lamellar arrays of membrane enclosed cristernae were found in fibers denervated for 11 weeks or longer. Lamellar structure may be derived from the element of sarcoplasmic reticulum. Focal dissociation of the basement membrane from the plasma membrane is observed in muscle fibers denervated 11 weeks or longer. The number of myofilament remarkably decreases and Z-zone of myofibril seems to be indistinct. The nuclear membrane is found to be somewhat irregular in contour. Relatively clear areas of sarcoplasm appear in the perinuclear zone and the enlarged sarcotubles. Clamps of mitochondria, lysosomes and vacuoles are seen in the perinuclear area as well as in the interior of the fibers. At a motor-endplate region, the presynaptic membrane and cytoplasma of nerve-ending show degenerative changes and the basement membrane structure in postsynaptic membrane is found to be swelling and clouding in contour.
After nerve section, a reduction of myoglobin content, succinic dehydrogenase and cytochrome oxidase activity occurs in 2 weeks. Myosin-ATPase activity does not decrease in the muscle at a time when there has been a great decline in the succinic dehydrogenase activity of mitochondria of muscle. Sarcolemma-ATPase activity examined by electronmicroscopic method, is found to reduce to the level, leading to the changes of potassium concentration in denervated muscle.
Acetylcholinesterase is localized in the postsynaptic space and also in the axon-Schwann interface. In denervated muscle, a reduced acetylcholinesterase activity may explain the phenomenon of denervation hypersensitivity. There is, however, no parallelism between the reduced acetylcholinesterase activity and the hypersensitivity of muscle to acetylcholine.