A roadmap for potassium buffering/dispersion via the glial network of the CNS

Abstract

Glia use multiple mechanisms to mediate potassium fluxes that support neuronal function. In addition to changes in potassium levels within synapses, these ions are dynamically dispersed through the interstitial parenchyma, perivascular spaces, leptomeninges, cerebrospinal fluid, choroid plexus, blood, vitreous, and endolymph. Neural circuits drive diversity in the glia that buffer potassium and this is reciprocal. Glia mediate buffering of potassium locally at glial-neuronal interfaces and via widespread networked connections. Control of potassium levels in the central nervous system is mediated by mechanisms operating at various loci with complexity that is difficult to model. However, major components of networked glial buffering are known. The role that potassium buffering plays in homeostasis of the CNS underlies some pathologic phenomena. An overview of potassium fluxes in the CNS is relevant for understanding consequences of pathogenic sequence variants in genes that encode potassium buffering proteins. Potassium flows in the CNS are described as follows: K1, the coordinated potassium fluxes within the astrocytic cradle around the synapse; K2, temporary storage of potassium within astrocytic processes in proposed microdomains; K3, potassium fluxes between oligodendrocytes and astrocytes; K4, potassium fluxes between astrocytes; K5, astrocytic potassium flux mediation of neurovasular coupling; K6, CSF delivery of potassium to perivascular spaces with dispersion to interstitial fluid between astrocytic endfeet; K7, astrocytic delivery of potassium to CSF and K8, choroid plexus (modified glia) regulation of potassium at the blood-CSF barrier. Components, mainly potassium channels, transporters, connexins and modulators, and the pathogenic sequence variants of their genes with the associated diseases are described.

Keywords: Glial network; Glial syncytium; Homeostasis; Ion channels; Potassium flux; Sleep; Spatial potassium buffering.