THE EFFECTS OF A CARDIAC GLYCOSIDE ON SUBCELLULAR STRUCTURES WITHIN NERVE CELLS AND THEIR PROCESSES IN SYMPATHETIC GANGLIA AND SKELETAL MUSCLE

Nerve cells and their processes in cat sympathetic ganglia and frog skeletal muscle have shown on electron microscopic examination alterations in subcellular morphology as a result of treatment with digoxin. Non-nervous cells were unaffected by the drug. These changes included, in ganglia, swelling of the affected cells, shrinkage of mitochondria with pronounced increase in internal density, swelling of Nissl substance in nerve cell bodies, and loss of structural detail in nerve processes. At the myoneural junction the motor nerve endings were swollen, mitochondria were altered, and the synaptic vesicles were reduced in numbers, those that remained being swollen. These changes were accompanied by invagination of the axon surface by Schwann cell processes.Cell swelling, but not the subcellular changes, was prevented by substitution of sulphate for chloride ions in the extracellular space. When the extracellular sodium ion concentration was reduced to 20 meq/l. the cells were completely protected against digoxin. It is concluded that swelling is caused by net uptake of sodium and chloride as a result of the known inhibitory action of digoxin on sodium extrusion by nerve cells. The possibility that these structural changes in subcellular organelles may be caused by a raised concentration of intracellular sodium ions, such as might occur during activity of excitable cells, is discussed.