Abstract
Astrocytes are the most abundant cell type in the CNS (central nervous system). They exert multiple functions during development and in the adult CNS that are essential for brain homeostasis. Both cation and anion channel activities have been identified in astrocytes and it is believed that they play key roles in astrocyte function. Whereas the proteins and the physiological roles assigned to cation channels are becoming very clear, the study of astrocytic chloride channels is in its early stages. In recent years, we have moved from the identification of chloride channel activities present in astrocyte primary culture to the identification of the proteins involved in these activities, the determination of their 3D structure and attempts to gain insights about their physiological role. Here, we review the recent findings related to the main chloride channels identified in astrocytes: the voltage-dependent ClC-2, the calcium-activated bestrophin, the volume-activated VRAC (volume-regulated anion channel) and the stress-activated Maxi-Cl−. We discuss key aspects of channel biophysics and structure with a focus on their role in glial physiology and human disease.
Highlights
Chloride is the main physiological anion, serving as the principal compensatory ion for the movement of major cations such as Na+, K+ and Ca2+ [1,2]
From among the different families of chloride channel activities with known proteins, here we review the main chloride channels found in astrocytes with a focus on their structure and their impact on astroglial physiology and disease
The possible contribution of the Volume-Regulated Anion-Channel (VRAC) to the process remains unknown, it is expected that the net influx of KCl during K+-siphoning could trigger astrocyte swelling through alterations in osmotic gradients, raising the possibility that VRAC activity plays a role in controlling neuronal excitability
Summary
Chloride is the main physiological anion, serving as the principal compensatory ion for the movement of major cations such as Na+, K+ and Ca2+ [1,2]. Astrocytes play a crucial role in the maintenance of the blood–brain barrier (BBB), and regulate the energetic metabolism coupling cerebral blood flow to neuronal needs and increasing the availability of oxygen and glucose [8,9,10]. They can enhance the exchange of soluble substrates between the CSF and interstitial fluid in the brain in a process named glymphatic flow [11,12,13]. From among the different families of chloride channel activities with known proteins, here we review the main chloride channels found in astrocytes with a focus on their structure and their impact on astroglial physiology and disease
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