On the metabolic basis of nervous activity

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Abstract
1. A study has been made of the metabolic substrates that can support the active extrusion of sodium ions from mammalian non-myelinated nerve fibres. The post-tetanic hyperpolarization obtained in chloride-free Locke solution, which reflects the electrogenic component of the sodium pump, was used as the index of metabolic activity.2. When glucose was removed from the Locke solution there was no immediate change in the size of the post-tetanic hyperpolarization.3. However, glucose is essential for metabolism in nerve fibres; for when a competitive inhibitor, deoxy-D-glucose, was added to the Locke solution the post-tetanic response was much reduced or abolished. Larger concentrations of deoxy-D-glucose were required in the presence of glucose than in its absence.4. This effect of deoxy-D-glucose could be reversed by glucose, fructose, pyruvate and acetate.5. The depressant effect of deoxy-D-glucose was enhanced by oxaloacetate and by malate.6. Malonate, a competitive inhibitor of the conversion of succinate to fumarate, reduced or abolished the post-tetanic hyperpolarization.7. This effect of malonate could be overcome by glucose and by pyruvate.