Metabolic Constraints on Neuronal Signaling

Abstract

Neuronal tissues process information through action potential generation and transmission. Reduced ionic gradients can significantly alter cellular function and signaling, and these gradients are reestablished through the conversion of ATP to ADP by the Sodium/Potassium pump. In order to investigate the constraints on neuronal computation, we used a conductance-based model incorporating ionic dynamics and a simplified version of glucose metabolism. The experiments suggest a programmed response to prolonged stimulation where the cell consumes more oxygen and excretes more potassium early on before switching to reduced ionic responses with decreased oxygen consumption. Using the model to correlate with experimental results from stimulated neuronal tissue, we demonstrated that the interplay between electrochemical dynamics of the cell naturally gives rise to the time-dependent nature of the experimental observations. The model revealed that a reduction in action potential generation occurs due to a gradual decrease in the resting transmembrane voltage. The hyperpolarization of the resting potential is due to the increase in intracellular sodium and extracellular potassium concentrations driving the Sodium/Potassium pump. The subsequent reduction of spike generation enables the pump to outstrip the sodium accumulation, causing a change in behavior of both the extracellular potassium and intracellular sodium concentrations.