Dependence of spontaneous neuronal firing and depolarisation block on astroglial membrane transport mechanisms
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Exposed to a sufficiently high extracellular potassium concentration ([K + ]o), the neuron can fire spontaneous discharges or even become inactivated due to membrane depolarisation (‘depolarisation block’). Since these phenomena likely are related to the maintenance and propagation of seizure discharges, it is of considerable importance to understand the conditions under which excess [K + ]o causes them. To address the putative effect of glial buffering on neuronal activity under elevated [K + ]o conditions, we combined a recently developed dynamical model of glial membrane ion and water transport with a Hodgkin–Huxley type neuron model. In this interconnected glia-neuron model we investigated the effects of natural heterogeneity or pathological changes in glial membrane transporter density by considering a large set of models with different, yet empirically plausible, sets of model parameters. We observed both the high [K + ]o-induced duration of spontaneous neuronal firing and the prevalence of depolarisation block to increase when reducing the magnitudes of the glial transport mechanisms. Further, in some parameter regions an oscillatory bursting spiking pattern due to the dynamical coupling of neurons and glia was observed. Bifurcation analyses of the neuron model and of a simplified version of the neuron-glia model revealed further insights about the underlying mechanism behind these phenomena. The above insights emphasise the importance of combining neuron models with detailed astroglial models when addressing phenomena suspected to be influenced by the astroglia-neuron interaction. To facilitate the use of our neuron-glia model, a CellML version of it is made publicly available.
KeywordsPotassium dynamics Positive feedback Spontaneous discharges Depolarisation block Glia
We are grateful for the assistance of Pulasthi Mithraratne in the creation of the diagram in Fig. 1. We are also indebted to John Wyller for helpful discussions, and to Maxim Bazhenov, Giri Krishnan as well as two anonymous reviewers whose comments and suggestions helped improve the quality of the paper. The research has been partially supported by the Research Council of Norway through grants no 178143 and 178892.
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