Gap junction coupling confers isopotentiality on astrocyte syncytium

Astrocytes are extensively coupled through gap junctions into a syncytium. However, the basic role of this major brain network remains largely unknown. Using electrophysiological and computational modeling methods, we demonstrate that the membrane potential (V_M) of an individual astrocyte in a hippocampal syncytium, but not in a single, freshly isolated cell preparation, can be well-maintained at quasi-physiological levels when recorded with reduced or K⁺ free pipette solutions that alter the K⁺ equilibrium potential to non-physiological voltages. We show that an astrocyte's associated syncytium provides powerful electrical coupling, together with ionic coupling at a lesser extent, that equalizes the astrocyte's V_M to levels comparable to its neighbors. Functionally, this minimizes V_M depolarization attributable to elevated levels of local extracellular K⁺ and thereby maintains a sustained driving force for highly efficient K⁺ uptake. Thus, gap junction coupling functions to achieve isopotentiality in astrocytic networks, whereby a constant extracellular environment can be powerfully maintained for crucial functions of neural circuits.