Astrocytic potassium and calcium channels as integrators of the inflammatory and ischemic CNS microenvironment

Abstract

Astrocytes are key regulators of their surroundings by receiving and integrating stimuli from their local microenvironment, thereby regulating glial and neuronal homeostasis. Cumulating evidence supports a plethora of heterogenic astrocyte subpopulations that differ morphologically and in their expression patterns of receptors, transporters and ion channels, as well as in their functional specialisation. Astrocytic heterogeneity is especially relevant under pathological conditions. In experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), morphologically distinct astrocytic subtypes were identified and could be linked to transcriptome changes during different disease stages and regions. To allow for continuous awareness of changing stimuli across age and diseases, astrocytes are equipped with a variety of receptors and ion channels allowing the precise perception of environmental cues. Recent studies implicate the diverse repertoire of astrocytic ion channels – including transient receptor potential channels, voltage-gated calcium channels, inwardly rectifying K+ channels, and two-pore domain potassium channels – in sensing the brain state in physiology, inflammation and ischemia. Here, we review current evidence regarding astrocytic potassium and calcium channels and their functional contribution in homeostasis, neuroinflammation and stroke.

A dietary polyphenol metabolite alters CA1 excitability ex vivo and mildly affects cortico-hippocampal field potential generators in anesthetized animals

“…1996 ). Interestingly, both astrocytes and microglial cells are known to express a variety of membrane channels similar to those responsible for intrinsic properties in neurons ( Schmaul et al. 2021 ; Sarkar 2022 ; Wang et al.…”

Contribution of Axon Initial Segment Structure and Channels to Brain Pathology

“…Numerous studies point towards a crucial role of astrocytic ion channels linking the CNS microenvironment to astroglial responses, modulating health, inflammation, and ischemia. Even if astrocytes are non-excitable cells, these cells express a battery of potassium and calcium voltage-gated ion channels, as well as other ion channels that act as sensors and modulators [ 119 ]. Increased intracellular Ca 2+ promotes ATP release from astrocytes, which modulates neuronal excitability and decreases the conduction speed in myelinated axons through their action on A2aR receptors and HCN2 channels in the AIS and nodes of Ranvier [ 120 ].…”

Ion Channel Dysfunction in Astrocytes in Neurodegenerative Diseases

“…These cells are capable of transporting ions, taking up neurotransmitters and producing neurotrophic factors to maintain the function and homeostasis of the CNS, where astrocytic ion channels have a pivotal role ( Ikeshima-Kataoka, 2016 ; Verkhratsky and Nedergaard, 2018 ). Transient receptor potential (TRP) channels are a family of calcium ion (Ca 2+ ) channels responsible for the transport of Ca 2+ in the plasma membrane and endoplasmic reticulum (ER), maintaining astrocyte Ca 2+ homeostasis and dynamics ( Zhang and Liao, 2015 ; Lim et al, 2016 ; Schmaul et al, 2021 ). The sensitivity of KCa3.1 channels to Ca 2+ means they are capable of transporting potassium ion (K + ) in response to Ca 2+ fluctuations ( Yi et al, 2017 ).…”