Developmental maturation of activity-induced K + and pH transients and the associated extracellular space dynamics in the rat hippocampus

Abstract

Key points: Neuronal activity induces fluctuation in extracellular space volume, [K + ] o and pH o , the management of which influences neuronal function The neighbour astrocytes buffer the K + and pH and swell during the process, causing shrinkage of the extracellular space In the present study, we report the developmental rise of the homeostatic control of the extracellular space dynamics, for which regulation becomes tighter with maturation and thus is proposed to ensure efficient synaptic transmission in the mature animals The extracellular space dynamics of volume, [K + ] o and pH o evolve independently with developmental maturation and, although all of them are inextricably tied to neuronal activity, they do not couple directly. Abstract: Neuronal activity in the mammalian central nervous system associates with transient extracellular space (ECS) dynamics involving elevated K + and pH and shrinkage of the ECS. These ECS properties affect membrane potentials, neurotransmitter concentrations and protein function and are thus anticipated to be under tight regulatory control. It remains unresolved to what extent these ECS dynamics are developmentally regulated as synaptic precision arises and whether they are directly or indirectly coupled. To resolve the development of homeostatic control of [K + ] o , pH, and ECS and their interaction, we utilized ion-sensitive microelectrodes in electrically stimulated rat hippocampal slices from rats of different developmental stages (postnatal days 3–28). With the employed stimulation paradigm, the stimulus-evoked peak [K + ] o and pH o transients were stable across age groups, until normalized to neuronal activity (field potential amplitude), in which case the K + and pH shifted significantly more in the younger animals. By contrast, ECS dynamics increased with age until normalized to the field potential, and thus correlated with neuronal activity. With age, the animals not only managed the peak [K + ] o better, but also displayed swifter post-stimulus removal of [K + ] o , in correlation with the increased expression of the α1-3 isoforms of the Na + /K + -ATPase, and a swifter return of ECS volume. The different ECS dynamics approached a near-identical temporal pattern in the more mature animals. In conclusion, although these phenomena are inextricably tied to neuronal activity, our data suggest that they do not couple directly.