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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. Full article

Due to strong electrical coupling, syncytial isopotentiality emerges as a physiological mechanism that coordinates astrocytes into a highly efficient system in brain homeostasis. Although this electrophysiological phenomenon has now been observed in astrocyte networks established by different astrocyte subtypes, the spinal cord remains a brain region that is still unexplored. In ALDH1L1-eGFP transgenic mice, astrocytes can be visualized by confocal microscopy and the spinal cord astrocytes in grey matter are organized in a distinctive pattern. Namely, each astrocyte resides with more directly coupled neighbors at shorter interastrocytic distances compared to protoplasmic astrocytes in the hippocampal CA1 region. In whole-cell patch clamp recording, the spinal cord grey matter astrocytes exhibit passive K⁺ conductance and a highly hyperpolarized membrane potential of −80 mV. To answer whether syncytial isopotentiality is a shared feature of astrocyte networks in the spinal cord, the K⁺ content in a physiological recording solution was substituted by equimolar Na⁺ for whole-cell recording in spinal cord slices. In uncoupled single astrocytes, this substitution of endogenous K⁺ with Na⁺ is known to depolarize astrocytes to around 0 mV as predicted by Goldman–Hodgkin–Katz (GHK) equation. In contrast, the existence of syncytial isopotentiality is indicated by a disobedience of the GHK predication as the recorded astrocyte’s membrane potential remains at a quasi-physiological level that is comparable to its neighbors due to strong electrical coupling. We showed that the strength of syncytial isopotentiality in spinal cord grey matter is significantly stronger than that of astrocyte network in the hippocampal CA1 region. Thus, this study corroborates the notion that syncytial isopotentiality most likely represents a system-wide electrical feature of astrocytic networks throughout the brain. Full article