The slow dynamics of intracellular sodium concentration increase the time window of neuronal integration: A simulation study

Changes in intracellular Na⁺concentration ([Na⁺]_i) are rarely taken into account when neuronal activity is examined. As opposed to Ca²⁺, [Na⁺]_idynamics are strongly affected by longitudinal diffusion, and therefore they are governed by the morphological structure of the neurons, in addition to the localization of influx and efflux mechanisms. Here, we examined [Na⁺]_idynamics and their effects on neuronal computation in three multi-compartmental neuronal models, representing three distinct cell types: accessory olfactory bulb (AOB) mitral cells, cortical layer V pyramidal cells, and cerebellar Purkinje cells. We added [Na+]i as a state variable to these models, and allowed it to modulate the Na⁺ Nernst potential, the Na⁺-K⁺pump current, and the Na⁺-Ca2⁺exchanger rate. Our results indicate that in most cases [Na⁺]_idynamics are significantly slower than [Ca²⁺]_idynamics, and thusmay exert a prolonged influence on neuronal computation in a neuronal type specific manner. We show that [Na⁺]_idynamics affect neuronal activity via three main processes: reduction of EPSP amplitude in repeatedly active synapses due to reduction of the Na⁺Nernst potential; activity-dependent hyperpolarization due to increased activity of the Na⁺-K⁺pump; specific tagging of active synapses by extended Ca²⁺elevation, intensified by concurrent back-propagating action potentials or complex spikes. Thus, we conclude that [Na⁺]_idynamics should be considered whenever synaptic plasticity, extensive synaptic input, or bursting activity are examined.