Spatial and Temporal Regulation of K+ Buffering in Hippocampal Astrocytes

Distinct subregions within the same structure (such as along the dorsoventral axis of the hippocampus) can exhibit unique molecular and physiological properties that relate to their functional specificity. These properties can be further modulated by circadian cycles. Understanding how extracellular potassium (K⁺) is regulated within this complex spatial and temporal framework is essential, as K⁺ dynamics directly influence neuronal excitability in both health and disease. Here, we reveal that hippocampal K⁺ dynamics exhibit pronounced subregional modulation and circadian specificity, with the ventral hippocampus (VH) showing faster K⁺ clearance than the dorsal hippocampus (DH), despite reduced functional Kir4.1 currents in VH astrocytes. This interplay between subregional organization, circadian regulation, astroglial K⁺ signaling, and Kir4.1 function provides new insights into the homeostatic control of hippocampal K⁺, offering a framework for understanding space- and time-dependent dysfunction in conditions such as epilepsy.