Neuromodulation of Astrocytic K+ Clearance

Abstract

Potassium homeostasis is fundamental for brain function. Therefore, effective removal of excessive K+ from the synaptic cleft during neuronal activity is paramount. Astrocytes play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]o) or impairments of the astrocytic clearance mechanism affect the resonance and oscillatory behavior of both the individual and networks of neurons. These results indicate that astrocytes have the potential to modulate neuronal network activity, however, the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behavior, on the astrocytic clearance process. Our results suggest that while some neuromodulators (5-HT; NA) might affect astrocytic spatial buffering via gap-junctions, others (DA; Histamine) primarily affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to maximize the synchronous network activity.

Astrocytes Exhibit a Protective Role in Neuronal Firing Patterns under Chemically Induced Seizures in Neuron–Astrocyte Co-Cultures

“…Furthermore, they uptake the excessive glutamate through glutamate transporters [ 61 ]. The cleared K + and glutamate are successfully buffered to distal areas through GJs [ 3 , 15 , 62 ]. The effect of the blockade of voltage-gated K + channels by 4-AP is assumingly counteracted by the astrocytic K + and glutamate buffering, which leads to statistically insignificant changes in our recorded activity features, such as SRs, BRs, IBIs, and burst durations.…”

Selective Involvement of a Subset of Spinal Dorsal Horn Neurons Operated by a Prodynorphin Promoter in Aβ Fiber-Mediated Neuropathic Allodynia-Like Behavioral Responses in Rats

“…Furthermore, voltage-gated K + channels or leak K + current through two-pore domain K + channels influence RMPs (Wulff et al, 2009 ; Blankenship et al, 2013 ). Further, it is known that astrocytes are activated after PNI (Tsuda et al, 2011 ; Kohro et al, 2015 ) and are involved in the clearance of extracellular K + (Bellot-Saez et al, 2021 ). Thus, activated astrocytes may be involved in the hyperexcitability of AAV-PdynP + neurons after PNI via a change in extracellular K + concentration.…”

First Responders to Hyperosmotic Stress in Murine Astrocytes: Connexin 43 Gap Junctions Are Subject to an Immediate Ultrastructural Reorganization

“…Although both studies demonstrate an inhibitory effect of hyperosmolar solutions on gap junctional function, they do not refer to associated changes in gap junction ultrastructure. In terms of the experimental design of this study, it would be desirable to dye-inject astrocytes in situ, combined with determination of the potassium clearance [ 56 ]. This approach would provide more detailed information on the link of hyperosmolarity and gap junction function [ 56 ].…”

“…In terms of the experimental design of this study, it would be desirable to dye-inject astrocytes in situ, combined with determination of the potassium clearance [ 56 ]. This approach would provide more detailed information on the link of hyperosmolarity and gap junction function [ 56 ]. Alternatively, patch clamp-based approaches could be used for electrophysiological recordings, possibly followed by the addition of gap junction-permeable tracers to visualize the cellular network [ 57 ].…”