Epileptiform Neuronal Discharges Impair Astrocyte Syncytial Isopotentiality in Acute Hippocampal Slices

Astrocyte syncytial isopotentiality is a physiological mechanism resulting from a strong electrical coupling among astrocytes. We have previously shown that syncytial isopotentiality exists as a system-wide feature that coordinates astrocytes into a system for high efficient regulation of brain homeostasis. Neuronal activity is known to regulate gap junction coupling through alteration of extracellular ions and neurotransmitters. However, the extent to which epileptic neuronal activity impairs the syncytial isopotentiality is unknown. Here, the neuronal epileptiform bursts were induced in acute hippocampal slices by removal of Mg²⁺ (Mg²⁺ free) from bath solution and inhibition of γ-aminobutyric acid A (GABA_A) receptors by 100 µM picrotoxin (PTX). The change in syncytial coupling was monitored by using a K⁺ free-Na⁺-containing electrode solution ([Na⁺]_p) in the electrophysiological recording where the substitution of intracellular K⁺ by Na⁺ ions dissipates the physiological membrane potential (V_M) to ~0 mV in the recorded astrocyte. However, in a syncytial coupled astrocyte, the [Na⁺]_p induced V_M loss can be compensated by the coupled astrocytes to a quasi-physiological membrane potential of ~73 mV. After short-term exposure to this experimental epileptic condition, a significant closure of syncytial coupling was indicated by a shift of the quasi-physiological membrane potential to -60 mV, corresponding to a 90% reduction of syncytial coupling strength. Consequently, the closure of syncytial coupling significantly decreased the ability of the syncytium for spatial redistribution of K⁺ ions. Altogether, our results show that epileptiform neuronal discharges weaken the strength of syncytial coupling and that in turn impairs the capacity of a syncytium for spatial redistribution of K⁺ ions.